International Conference on Brain Disorders and Therapeutics August 24-26, 2015 London, UK

Biography:

In 1993 Kerensa started her study nutrition and dietetics in Amsterdam. After finishing the bachelor in 1997, she continued with a master degree nutrition and food management at Huddersfield University in the UK. From 2000 until 2005 she worked as a PhD student at Wageningen University on the biophysics of unfolding, refolding and aggregation of food related proteins. Her first postdoctoral work was at the Medical Research Council – Laboratory of Molecular Biology in the Neurobiology department in Cambridge, UK. This work focused on fatty acid – a-synuclein interactions employing both biophysics and cell culture as research tools. Her second postdoc was at the Free University of Brussels (VUB) in Belgium where she started working on the role of amyloid beta peptide in Alzheimer’s disease. Here she also obtained an Odysseus grant from the Belgian government and, as a result of that, was offered a position as assistant professor. Kerensa moved to her current position as an assistant professor at the University of Twente in March 2011. She prefers to spend her spare time in the dojo doing karate, travelling, gardening or reading.

Abstract:

Soluble aggregated forms of the beta amyloid peptide (Aβ) have been shown to play an important role in the progress of Alzheimer disease. This extracellular residing peptide arises from cleavage of transmembrane amyloid precursor protein through cleavage by means of a combination of secretase enzymes. As a result of this enzymatic processing, genetic profile and further modifications, the amyloid beta peptide does not exist as a well-defined species but arises in a variety of truncated and modified forms. For example, it has been reported that, within any one individual, a range of amyloid beta peptides exist varying in length from 34 to 49 amino acids and that multiple otherwise modified forms of this peptide are present in a complex mixture. By simple mixing of various ratios of Aβ1-40 and Aβ1-42, the two most prominent forms of the peptide present in the brain, we have already shown that small shifts in the ratio between these two peptides can have significant impact on the aggregation reaction, cellular response and cognitive behavior in animal models (1,2). These shifts are of biological relevance as it has also been reported that the presence of longer and more aggregation-prone Aβ1-42 slightly rises in patients with Alzheimer disease, sometimes at the cost of Aβ1-40 production. We extended our observations by also including Aβ1-38 and Aβ1-43 into the equation and found that inclusion of these peptides can alter the toxic profile of these peptides (3). Further investigations into disease-related mutations related to deposition of the peptide into the vascular system showed that fibrillar structures of the peptide assume a structure that deviates from the wild type morphology of which the contribution to disease have yet to be determined (4). From these examples and other investigations into this topic we concluded that the complexity of the amyloid beta peptide mixture should be acknowledged upon investigating the contribution of this peptide toward disease and development of potential therapeutic developments. During my talk, I will provide an overview of our recent work on complex amyloid beta peptide mixtures and their potential contribution toward progress of Alzheimer disease.

Biography:

Hélène Castel started to develop different variants of the electrophysiological technique at the university of Rouen in the laboratory of Dr Vaudry (U413 Inserm) and biochemical approaches to give a comprehensive view of modulation of the GABAA receptor-channel function by interacting proteins. She received her PhD in Neurosciences, Molecular and Cell Biology at the Rouen University in 2000, and then spent 2 years on a post-doctoral position in Pr Colquhoun’s laboratory at University College of London, UK. There, she has developed fast-concentration-jump techniques to mimic electrical fast synaptic inputs on recombinant NMDA receptors and acquired expertise in molecular biology through mutagenesis of NMDA receptor subunits. In 2002, she obtained a permanent position as chargée de Recherche (CR) at the French National Institute of Health (Inserm) and University of Rouen. In 2010, she became group Leader “Astrocyte and Vascular Niche” and since 2015, she is co-head of the international platform “Cancer and Cognition” under the French North-West Canceropole. She develops projects based on vasoactive and chemokine G protein-coupled receptors (GPCRs) in tumor brain, brain vascular physiopathology and on cognitive dysfunctions induced by cancer and targeted therapies.

Abstract:

Subarachnoid haemorrhage (SAH) refers to extravasation of blood into the compartment between the brain and the tissue that covers the brain. This is often due to a ruptured aneurysm and accounts for up to 5% of all new stroke cases. Survivors of SAH commonly experience sequels that affect their day-to-day lives and which could persist years after; these include fatigue, memory deficits, executive function, language, depression and sleep disorders. The cerebral arterial vasospasm (CV) is a complication of the SAH, and may by associated with neurological deficits, microthrombosis and cerebral ischemia. Despite advances in diagnosis and surgical treatment, effective therapies are still limited and clinical outcomes remain disappointing. The CV may be due to vasoactive peptides which are released locally and which, under normal conditions, control the blood/brain exchange. One of the most potent vasoactive peptides is urotensin II (UII). Urotensin II (UII) and its paralog URP activate a G protein coupled receptor (GPCR) named UT. UII exerts a wide range of physiological effects and regulate the endocrine, cardiovascular, kidney and immune functions. Our study aimed at providing significant advances and proof of concept of a new therapeutic target in SAH in a major area of public health involving neurological disability and the dramatic change in the quality of life. We led a single-center prospective study over a period of 24 months, including all patients with SAH of aneurysmal origin with external ventricular bypass and aneurysm exclusion, classified stage 1 or 2 in the WFNS scale. Blood and CSF samples were collected from D0 to D8. The ROC curve showed that the plasma concentration of UII is a discriminating factor for the occurrence of CV (AUC 0.824, P = 0.02, patent FR1356995, 2013). A mouse model of SAH was also developed via a double injection of arterial blood into the magna cisterna during two consecutive days. Occurrence of CV of the cerebral middle, basilar and anterior arteries and a number deposition of fibrin (microthrombis) were observed from the 2nd to the 14th day post-SAH, as well as increase in the activity of caspase-3 from Day 3 to 14 in brain cortex, hippocampus, endothelium and choroid plexus. Impaired sensorimotor functions (beam walking test) were detected from D7 to D10. Then, we investigated the impact of the UII system in this SAH model my means of wild-type (UT+/+) and KO-UT (UT-/-) mice. UT-/- mice do not exhibit any remarkable phenotype. The β-galactosidase activity (reporter of the UT transcription) was very faint in the brain cortex, endothelium, and choroid plexus in Sham UT-/- mice and strong in brain cortex, hippocampus, choroid plexus and microvessels 10 days post-SAH. Consistent with these observations, we demonstrated the expression of UII peptide in the brain cortex, the hippocampus and in some large and small arteries only in SAH mice. Interestingly, the UT ligand urantide, listed so far as \"antagonist\", but now definitively characterized as a biased ligand1, completely prevented CV, microthrombosis and consecutive neurosensitivomotor deficits in SAH mice, suggesting that UT ligands may constitute interesting therapeutic tools. We should in the future, explore the effect of other UT biased ligands which may cross the blood brain barrier and bind UT, mainly expressed during the course of the SAH pathology. These compounds with minimal side effects can be extremely innovative in the treatment of SAH, but also in other cardiovascular pathologies.

Biography:

Mehrdad Shamloo has completed his PhD from University of Lund, Sweden. Since the inception of his doctoral studies in 1999, he has been working in the field of neuropharmacology and drug discovery and has led numerous industrial and NIH funded research projects in this field. Currently, he is Associate Professor of Neurosurgery and director of Behavioral and Functional Neuroscience Laboratory at Stanford University School of Medicine. He directs multiple preclinical and pharmacological drug discovery program with special focus on neuroprotective compounds, cognitive enhancers, and regenerative small molecules.

Abstract:

Despite a huge impact on both individuals and public health, Alzheimer\'s disease (AD) remains incurable without an effective, disease-modifying therapy. The lack of effective therapy in AD is attributable to the complex array of factors that are involved in its development and progression. β1-adrenergic receptor (β1-ADR) is promising neuropharmacological target for the treatment of AD. Dysfunction of β1-ADR and its downstream signaling cascade are strongly implicated in cognitive symptoms of AD. Besides its involvement in cognitive symptoms, deficiency of the endogenous ligand for β1-ADR, noradrenaline, is highly correlated with several pathological features of AD including tissue load of amyloid plaques and neurofibrillary tangles. The involvement of β1-ADR in multiple key aspects of AD is a unique and therapeutically attractive feature that could enable a comprehensive strategy toward the treatment and management of the disease. Importantly, recent studies from our laboratory have shown that stimulation of β1-ADR is a promising therapeutic strategy for AD. In two independent preclinical models of AD, we have shown that stimulation of β1-ADR with the partial agonist, xamoterol, restores the cognitive deficits associated with the disease. Moreover, the β1-ADR agonist xamoterol increases the microglia phagocytic activity as evident by increase in CD68 and reduces soluble form of amyloid beta peptide (AB1-40). These data suggest that pharmacological modulation of β1-ADR could provide a novel therapeutic strategy to provide comprehensive therapeutic benefit for AD by simultaneously addressing cognitive symptoms and underlying neuropathology.

Biography:

Amir Mufaddel has graduated from Khartoum University and had his MD in psychiatry from Sudan Medical Specialization Board in 2008. Currently working in AlAin hospital, Community Mental Health Services. He is an adjunct lecturer in United Arab Emirates University. He has published several papers in reputed journals mostly reflecting the psychiatric aspects of physical conditions such as neurology, infectious diseases and dermatology.

Abstract:

Background: Central nervous system (CNS) calcifications can occur in a wide range of conditions with different etiologies. Calcifications can occur as physiologic, dystrophic, congenital or vascular calcifications. Methods: The aim of this paper was to discuss differential diagnosis of psychiatric conditions associated with CNS calcifications. A literature review was conducted using the key words cerebral calcifications, basal ganglia calcifications, intraaxial calcifications, extra-axial calcifications and psychiatric symptoms. Type, duration, and course of psychiatric symptoms were reviewed. Results: Brain calcifications can occur as intra- or extra-axial calcifications. Structures commonly involved in intra-axial clarifications are the basal ganglia and the cerebellum. Calcifications can be idiopathic/genetic such as that occurring in Fahr’s disease. Psychiatric symptoms in individuals with basal ganglia calcifications can present with variable clinical features including cognitive decline, auditory hallucinations, delusions, irritability, aggression, depressed mood, anxiety, personality changes and suicidal thoughts. Psychiatric symptoms can be acute or chronic; and some patients received clinical psychiatric diagnoses including: dementia, schizophrenia-like psychosis, mood disorders, frontal lobe syndrome, and mental retardation. Extra-axial calcifications such as that occurring in falx cerebri and the pineal gland can also be associated with psychiatric symptoms. Rare conditions with falx cerebri calcifications such as Gorlin-Goltz syndrome can present with acute course or with relapses and remissions. Conclusion: Radiologic investigations are useful tools to exclude organic pathology in patients presenting with psychiatric symptoms. For psychiatric patients who present with CNS calcifications, the location of calcification and the clinical psychiatric and systemic presentation are of vital importance in diagnosis.

Biography:

Shahid Hussain Sheikh graduated his MBBS in 1980 and Ph.D. in Neurology in 2011. He served in various medical research positions at the Univ. of WA Med. Cntr. from 1982 to 1992. As a Professor of clinical Physiology in 1992 at American College of Prof. Edu., also served A.C. Med. Cntr, as a Research Scientist/ teaching faculty and clinical studies. He has pioneered unveiling of the proliferating viral RNA based clinical pathology of the affected nucleus of the controlling neurons.

Abstract:

The label of “Cerebral Palsy” has been used frivolously due to the lack of knowledge of the Brain’s pathology. Since 2004, a number of researchers have stumbled upon a new paradigm in the field of Neurology1 that now opens up a new door of hope to better the quality of life of the suffering infants, children and adolescence worldwide. Now, many children with CP are known to be suffering from the Neuronal Sub-Nucleus Neuro viral RNA proliferation that begins as early as the inception of a new baby. The genetically transforming diseases now take a back seat to this new revelation, where, the Neuro Viral RNA’s being part of the chromosomal DNA of the sperm or the Ovum also ready to proliferate in the developmental stage of the Neuro Disk of the fetus in the first trimester. Therefore, the brain, spinal cord and all nerves may have the greater architectural influence of the Neuro Viral RNA Proliferation. So much so that, this influence may be carried out in to the developing functions of the organelles, cells, membranes, tissues, organs, systems. All cells, membranes, tissues, organs and systems are constructed with the Sensory Nerves and Motor Nerves, therefore, connected and controlled by the peripheral and central nervous system. On the other hand, maternal Immunity interferes in the defense, so long to protect the developmental anomalies, equal to the potency of the hosting mother’s immunity. If the virion / RNA proliferation is faster than the production and potency of the immune cells, of course, the battle is going to be lost. Baby is going to be presenting the pregnancy related challenges, and if born, may have some serious developmental challenges. Any Neuronal anomaly among the billions of developing neurons will translate in to what we know today as the Cerebral Palsy, Late Milestone, Autism, Hydrocephaly etc. It is now discovered that Neuro Viral RNA proliferation does take place due to the auto immune disorder, in particular, the Neuro Immune Dysfunction Syndrome now further defined as “Sheikh’s Syndrome” (A Multi Neuronal Sub-Nucleus Neuro Viral RNA Proliferation).

Biography:

Wail M Hassan has completed his Bachelor’s degree in Microbiology and a Graduate Diploma in Public Health from Alexandria University in 1990 and 1993 respectively. He has completed his PhD in Microbiology from the University of Southern Mississippi in 2004. He has occupied several Post-doctoral positions between 2004 and 2010 at University of Colorado at Boulder, the National Naval Medical Center and University of Nebraska Medical Center. In 2011, he joined the University of Wisconsin-Milwaukee as an Assistant Professor where he continues his research focusing on the molecular mechanisms of amyloid beta toxicity.

Abstract:

Multiple genes have been linked to Alzheimer’s disease (AD) implicating multiple metabolic pathways in its pathogenesis. It is not clear, however which of these genes are involved in general stress response and which are linked to AD-specific pathologies. To make an attempt to answer this question, we investigated changes in gene expression induced by human β-amyloid peptide (Aβ) in a transgenic C. elegans Alzheimer’s disease model. Aβ-induced gene expression changes were compared to those caused by a synthetic aggregating protein to identify Aβ-specific genes. Among the Aβ-specific genes identified in this study were genes involved in aging, lifespan regulation, proteasome structure and function and mitochondrial function. Interestingly, a significant overlap between Aβ- and Cry5B (a bacterial pore-forming toxin) induced gene expression alterations was observed. Further testing suggested the involvement of membrane damage in Aβ pathogenesis. In this study, we segregated Aβ-specific gene expression changes from general stress response in a simple metazoan animal and provide evidence implicating membrane damage in Aβ toxicity. We hope this work will eventually help identify novel therapeutic targets and further our understanding of AD pathogenesis.

Biography:

Reeta Jaya Philip is a PhD scholar in Speech Language Pathology at Dr. S R Chandrasekhar Institute of Speech and Hearing, Bangalore University, India. Her area of research interest includes traumatic brain injury and related disorders and adult neurogenic language disorders.

Abstract:

Background: Traumatic brain injury (TBI) can have a major impact on an individual’s cognitive, social, physical, emotional and behavioral aspects. Management of Cognitive Communication Disorders (CCD) in individuals following traumatic brain injury is a clinical challenge. Aim: To highlight the use of test battery approach in substantiating the nature and severity of cognitive communication disorder subsequent to TBI. Method: The participant of this study is a 20 year old male who experienced traumatic brain injury due to road traffic accident. MRI revealed contusions in bilateral inferior frontal lobes. Neurosurgical management was bicoronal skin incision and bifrontal decompressive craniotomy. Participant underwent various neuro surgical procedures such as Bifrontal craniotomy and bilateral fronto-parietal craniotomy. The diagnostic test battery incorporated for the assessment was Mini Mental Status Examination, Addenbrook’s Cognitive Examination-Revised, Brief Test of Head Injury, Bililingual Aphasia Test. Results: Cognitive linguistic deficits were explored by using the test battery. Results revealed severe deficits in auditory comprehension, expression, attention, orientation, visuospatial functions, memory and problem solving. Code mixing and translation disorder was also seen in cross linguistic examination. Conclusion: Study highlighted the cognitive communication disorders in TBI. Clinical evaluations and neuro linguistic correlations were done. The results revealed the utility of test battery approach in exploring the complete nature of CCD in TBI. Results have implications for cognitive linguistic rehabilitation of TBI.

Biography:

Daly Sebastian is currently working as a junior Lecturer in Department of Speech Language Studies, Dr. S. R. Chandrasekhar Institute of Speech and Hearing, Bangalore University. Her areas of research interest are neurogenic communication disorders, Multilingualism and neuro cognition. She has published papers in reputed journals and contributed chapter in International text books.

Abstract:

Introduction: Aphasia defined as a multimodal loss of language is one of the most feared symptoms of stroke. About 21– 38% of acute stroke survivors suffer from aphasia. Boca’s aphasia is a classical form of expressive aphasia. Preserved auditory comprehension, impaired repetition, nonfluent speech and lesion in the foot of the third frontal convolution (Broca’s area, Broadmann’s no. 44) are classical features of Broca’s aphasia. Aim: (1) To investigate the relationship between phonological paraphasia and auditory temporal processing deficits in persons with Brocas’s Aphasia. (2) To investigate the role of auditory temporal training for the treatment of phonological paraphasia in persons with Bocas aphasia. Method: Participants: Twenty participants with a history of ischemic stroke in the left Middle Cerebral Artery and clinically diagnosed as Brocas Aphasia were selected for the study. Twenty participants were divided into two group based on their neurolinguistic features. There were a group of 10 aphasics with semanatic paraphasia and the other 10 with phonological paraphasia. Informed consent was taken from the participants and all the procedure were strictly adhered to ethical guidelines. Stimuli: Auditory temporal processing testing was carried out using a maximum likelihood procedure toolbox, which implements an MLP in MATLAB software. The participant’s ability to detect a temporal gap in the center of a 750 msec broadband noise was measured. The noise had 0.5 msec cosine ramps at the beginning and end of the gap. In a two-interval alternate forced choice protocol was used. Phase 1: Psycho acoustic evaluation of temporal processing was done by estimating gap detection threshold (GDT). Comparison was done between the semantic paraphasia group and phonological paraphasia group. GDT of both the groups were compared with the normal age matched subjects thresholds (which was obtained for the purpose of another study). Phase 2: Phonological paraphasia group was divided into two, group A and B with five participants in each group. Group A was taken as control group and Group B was taken as experimental group. Group B was given 15 hours of auditory temporal based cue training which included speech and non-speech stimuli with difference only in durational aspects. After 15 sessions of training group A and B were tested by using Gap detection test and percentage of phonological paraphasia was also calculated. Results: There was significant difference in the GDT scores of phonological paraphasia group and semantic paraphasia group (P<0.05). Phonological paraphasia group had poor GDT scores on the right ear which is opposite to the site of lesion. However, semantic paraphasia group had values similar to the normal participants. Within group investigation of temporal cue based training indicated that there were no substantial changes in GDT and percentage of phonological paraphasia (POP) of group A. However, GDT became improved for group B and POP was also reduced. Improved temporal resolution was seen in the right ear responses of Group B. Discussion: Our findings are emphasizing the need for viewing the deficits and rehabilitation options of persons with Brocasapahasia slightly different from a conventional view. Study give insight into the need for temporal cue based assessment and treatment options for persons with Broca’s Aphasia. The reason for the poor GDT of phonological paraphasia group was tried to explain based on the nature of site of lesion and recent evidences in the role of Brocas area in speech perception. Supporting evidences were taken from current models of brain language processing claim that several temporal, parietal and frontal areas interact in order to deliver the many features of language ability. Results were also supported by experience dependent neuroplasticity based research in aphasia. Current study attempted to highlight the need for translational research in aphasia also. The study will serve as a contemporary perspective in Aphasiology.

Biography:

Psychologist w firmie University of Social Sciences and Humanities

Abstract:

The research aims to investigate the functioning of the brain at an early age, while taking into consideration the role of working memory and stimulating the function. We explored the cognitive profiles of children with working memory impairments. In an initial screening of 180 six-year-olds and identified children with low working memory scores. The research includes 2 groups of children: active (with cognitive training) and passive (without cognitive training). Cognitive skills (Raven's Coloured Progressive Matrices (CPM) - psychological test, Antisaccades (AS) task, Memory Guided Saccades (MGS) – eye-tracking research, Test of Working Memory Capabilities (TOWMC), Test of Knowledge and Competences (TOKAC) were assessed before, after cognitive training and third time, tree months after cognitive training). The training took 8 weeks, 5 times a week, 15 – 20 minutes each day. We studied the hypothesis: 1.The improvement of the trained function of operational memory measured by the eye-tracker will be noted in all training groups, but a higher dynamic of progress will be observed among children with low working memory; 2. The transfer of the effects of cognitive training will be observed in eye-tracker, TOWMC and TOKAC data, but among children with low working memory it will be more differentiated, than among healthy children; 3. The improvement of learning skills measured by TOKAC will be noted in all training groups, but a higher dynamic of progress will be observed among children with low working memory; 4. Durability of the training results on the operational memory’s functioning will be observed in all groups. The results of the research should serve as a basis for further studies, both cognitive and clinical. In cognitive studies, they should serve as a reference point to further studies into the role of working memory and cognitive training in early development stage. In clinical studies, the effects of the experiment can serve an important role in combining computer cognitive training with another treatment e.g. medication.

Biography:

Hans von Holst received his Medical Doctor´s degree in 1976 at Karolinska Institutet and completed his specialist training in Neurosurgery 1982 at Karolinska University Hospital. In 1985 he earned his PhD when he also became Associate Professor in Neurosurgery, Clinical Neuroscience at Karolinska Institutet. Since 1988 he holds a position as Senior Physician in Neurosurgery at Karolinska University Hospital. During 1991-1996 he was appointed as Chairman of the Dept of Neurosurgery and Division Manager of the Neuroclinics at Karolinska University Hospital, respectively. From 1992 to 2006 he was appointed as chairman of the World Health Organization collaborating center for neurotrauma at Karolinska Institutet. Since 2003 he is Professor in Neuroengineering and Head of the Division of Neuroengineering at the Royal Institute of Technology in Stockholm. He has over 120 original research publications, book chapters and books

Abstract:

Cytotoxic brain tissue edema is a complicated secondary consequence of ischemic injury following traumatic brain injury and stroke. The pathophysiological mechanisms are known to some extent but far from completely. A hypothesis has been proposed where protein unfolding and perturbation of nucleotide structures participate in the development of cytotoxic edema. The hypothesis is based on an advanced computational simulation model of the human head where a simulation of a traumatic brain injury was performed. The consequences of kinetic energy transfer following an external dynamic impact were analyzed including the intracranial pressure (ICP), strain level, and their potential influences on the noncovalent and covalent bonds in folded protein structures. It was shown that although most of the transferred kinetic energy is absorbed in the skin and three bone layers. It was further discovered that a substantial amount of kinetic energy reached the the brain tissue in gray and white matter. Thus, the kinetic energy from a dynamic impact has the theoretical potential to interfere not only with noncovalent but also covalent bonds when high enough. The induced mechanical strain and pressure may further interfere with the proteins. Simultaneously, the noncovalent energy rich bonds in nucleotide adenosine-triphosphates may be perturbed as well. The subsequent attraction of increased water molecules into the unfolded protein structures and disruption of adenosine- triphosphate bonds could to some extent explain the etiology to cytotoxic edema. Based on the new hypothesis and knowledge it is realistic to change the neurosurgical treatment of today by using neuroengineering simulations already before a neurosurgical procedure is taking place. Further development of the innovative hypothesis makes it possible to open up for new drug and infusion treatment aiming at redicing the severe consequences of cytotoxic brain tissue edema.

Biography:

Miriam Furst received the B.Sc. and M.Sc. degrees in applied mathematics and the Ph.D. degree in biomedical engineering from Tel Aviv University, Ramat Aviv, Israel, in 1973, 1975, and 1981 respectively. From 1982 to 1984, she was a Post-DoctoralFellow in the Research Laboratory of Electronics, Massachusetts Institute of Technology (MIT), Cambridge. Since 1984, she has been a faculty member with the Department of Electrical Engineering Systems, Tel Aviv University. Her main research interest is the auditory system as part of a wider interest in human communication channels. She has published more than 50 papers.

Abstract:

Multiple sclerosis (MS) is a disease that is both a focal inflammatory and a chronic neurodegenerative disease. The focal inflammatory component is characterized by destruction of central nervous system myelin including the spinal cord; as such it can impair any central neural system including the auditory system. While on the one hand auditory complaints in MS patients are rare compared to other senses, such as vision and proprioception, on the other hand auditory tests of precise neural timing are never “silent.” Whenever focal MS lesions are detected involving the pontine auditory pathway, auditory tests requiring precise neural timing are always abnormal. Azimuth sound localization is accomplished by comparing the timing and loudness of the sound at the two ears. Hence tests of azimuth sound localization must obligatorily involve the central nervous system and particularly the brainstem. Whenever a focal lesion was localized to the pontine auditory pathway, timing tests were always abnormal. A timing test that included only high frequency sounds was very often abnormal even when there was no detectable focal MS lesion involving the pontine auditory pathway. This test may be a marker for the chronic neurodegenerative aspect of MS, and, as such could be used to complement the MRI scan in monitoring the neurodegenerative aspect of MS. Studies of MS brainstem lesion location and auditory function have led to advances in understanding how the human brain processes sound. The brain processes binaural sounds independently for time and level in a two stage process. The first stage is at the level of the superior olivary complex (SOC) and the second at a level rostral to the SOC.

Biography:

Alex Bekker is an internationally recognized expert in neuroanesthesia and is frequently invited to speak at Grand Rounds and Scientific Panels. He has been active in research for many years. He is the author of 62 peer reviewed publications, 6 US patents, 32 educational reviews and more than 100 abstracts. His work has focused on perioperative brain protection, neuroinflammation, and clinical pharmacology. He was a PI of numerous clinical trials, including studies sponsored by the National Institute of Aging. He serves on the editorial board of the Journal of Neurosurgical Anesthesiology and is an ad hoc reviewer for 15 peer-reviewed journals, including NEJM, Anesthesiology, Neurosurgery, and Anesthesia and Analgesia. He is spearheading a campaign to improve the efficiency of Perioperative Services as well as Patient Safety at the University Hospital

Abstract:

Perioperative stroke is defined as an episode of focal or global loss of cerebral function with symptoms lasting more than 24 hours. Perioperative strokes result in increased duration of hospital stay, rates of disability, discharge to long-term care facilities and death after surgery. General surgical procedures are associated with a 0.08-0.7% risk of stroke. The incidence is higher for coronary artery bypass grafting surgery (1.4-3.8%) and valve replacement surgery (up to 9.7%). Potential stroke etiology includes hypoperfusion (global and focal), thromboembolism and hemorrhage. The preoperative patient related risk factors for perioperative stroke are advanced age, previous cerebrovascular diseases, peripheral vascular disease, chronic obstructive pulmonary disease (COPD), atrial fibrillation, hypertension, cardiac valvular disease, diabetes mellitus, HTN, atherosclerosis and renal disease. General anesthesia, dehydration, bed rest, stasis in the postoperative period and perioperative withholding of antiplatelet or anticoagulation agents can aggravate surgery-induced hypercoagulability and increase the risk of perioperative thrombogenic events. Elective surgery should be delayed for at least 1 month after a documented ischemic stroke. Another consideration in the preoperative period is patients who require chronic anticoagulation. Bridging oral anticoagulant therapy (warfarin) with heparin or low molecular weight heparin should be considered for the majority of patients who require temporary interruption of warfarin therapy. Several studies suggested that intraoperative hypotension induced by anesthesia does not considerably increase risk for perioperative stroke in patients with carotid disease. Most authors recommend that intraoperative blood pressure should be maintained within 20% of preoperative level.Postoperative risk factors for a stroke include heart failure, myocardial infarction, arrhythmias (atrial fibrillation), dehydration (blood loss) and hyperglycemia. Anticoagulation in the immediate postoperative period especially in patients with AF may be useful.Implementation of the therapeutic measures that reduce the incidence of this complication is an appealing concept because failure of neuroprotective agents in acute stroke may be due to delay in presentation after stroke has occurred. Preoperative administration of statins, ASA, a continuation of anticoagulation therapy (when indicated) as well as appropriate timing of surgery do appear to reduce the incidence of stroke after CABG and vascular surgery and may show similar results in the general surgery population as well. Anesthesiologists can implement several therapeutic and procedural measures to minimize morbidity associated with a perioperative stroke.

Biography:

Michihiko Koeda is a senior assistant professor of the psychiatry department at Nippon Medical School, Tokyo, Japan. He completed his PhD at the Medical Research Institute of Tokyo Medical and Dental University. He was a visiting researcher at the University of Glasgow. He is continuing to investigate auditory brain function by the use of functional MRI to clarify the pathophysiology of psychiatric symptoms, and pharmacological and/or genetic effects

Abstract:

Greeting conversations are essential tools for communicating socially with family, friends, and community. Attractiveness is one of the favorable behaviors associated with social communication. A recent study showed that the roles of inferior frontal gyrus (IFG) and superior temporal gyrus (STG) are essential for perceiving auditory attractiveness. However, to our knowledge, no study has ever investigated the cerebral response to auditory attractiveness in schizophrenia. We aimed to clarify the cerebral function underlying the perception of auditory attractiveness in schizophrenia patients. Cerebral activation was examined in 18 schizophrenia patients and 18 controls when performing Favorability Judgment Task (FJT) and Gender Differentiation Task (GDT) for pairs of greetings using event-related functional MRI. Full-factorial analysis revealed that the main effect of task was associated with activation of left IFG and STG. The main effect of Group revealed less activation of left STG in schizophrenia compared with controls, whereas significantly greater activation in schizophrenia than in controls was revealed at left middle frontal gyrus (MFG), right temporo-parietal junction (TPJ), right occipital lobe, and right amygdala (p<0.05, FDR-corrected). A significant positive correlation was observed at right TPJ and right MFG between cerebral activation under FJT minus GDT contrast and the score of hallucinatory behavior on the Positive and Negative Symptom Scale. Findings of hypoactivation in left STG could indicate brain dysfunction in accessing vocal attractiveness in schizophrenia, whereas hyperactivation in right TPJ and MFG may reflect the process of mentalizing other person’s behavior by auditory hallucination by abnormality of cognitive bias.

Biography:

Amir Mufaddel has graduated from Khartoum University and had his MD in psychiatry from Sudan Medical Specialization Board in 2008. Currently working in AlAin hospital, Community Mental Health Services. He is an adjunct lecturer in United Arab Emirates University. He has published several papers in reputed journals mostly reflecting the psychiatric aspects of physical conditions such as neurology, infectious diseases and dermatology.

Abstract:

The relation between psychiatry and epilepsy remains one of the topics that has been continuously attracting attention in medical literature since the time of Hippocrates. Forced normalization was later conceptualized when biological treatment for psychiatric disorders was developed. Recently, several reports were published regarding possible adverse psychiatric effects of antiepileptic medications. The picture is further complicated by the fact that psychotropic medications, which may be used for treatment of psychiatric disorders in epilepsy, can have negative effects on seizure control. Psychiatric symptoms, in relation to seizure, can be categorized into the following types: pre-ictal, ictal, post-ictal, inter-ictal and ictal symptoms. Depression and anxiety are commonly associated with epilepsy and can occur in all of the above categories . Depression can be severe and suicidal behavior has been reported as one of the common psychiatric associations with epilepsy, and has also been linked to use of some antiepileptic drugs. Psychosis can occur as an acute or chronic form. Transient pleomorphic post-ictal psychosis particularly observed in those with hippocampal sclerosis. There is an increased risk of developing schizophrenia and schizophrenia-like psychosis in patients with epilepsy. Psychiatric symptoms can also emerge during use of some of the antiepileptic drugs. Adverse psychiatric events include depression, psychosis, suicidal risk, and cognitive impairment. On the other hand, some of the psychotropic medications are known to be epileptogenic. Therefore, selection of psychotropic medications should be based on their possible effects on seizures; and those known to be epileptogenic should be avoided.

Biography:

Theresa D Hernandez, Ph.D. has been studying traumatic brain injury (TBI) using basic and clinical neuroscience models since 1985. Her ongoing, extramurally funded research program assesses the degree to which recovery and functional outcome after TBI can be optimized in a variety of populations (Veterans, civilians, athletes). This includes conducting randomized, placebo-controlled, blinded trials of novel interventions, such as acupressure. This work is accomplished through her appointment as Professor and Chair of the Department of Psychology & Neuroscience at CU Boulder, her appointment as a Senior Investigator and Research Psychologist in the Eastern Colorado Healthcare System, Rocky Mountain MIRECC (Mental Illness, Research, Education & Clinical Center) and through her role as one of the co-Directors of the PAPRR (Promoting Athlete Performance, Recovery and Resilience) Board at CU Boulder. She is also the Director of the CAIRR (Clinical Assessment of Injury, Recovery and Resilience) Neuroscience Laboratory.

Abstract:

Objective: Presentation of current challenges and opportunities associated with CAM (complementary and alternative medicine) research and clinical applications in Civilian, Veteran and Military Service populations in the U.S. and Europe. Following a brief overview of CAM, there will be a discussion of translational capacity from basic to clinical research to clinical practice, as well as how to develop an adoptable evidence base, with proof of effectiveness. Methodological and ethical challenges associated with CAM research in those with traumatic brain injury and co-morbidities will also be described in terms of how these challenges relate to practice and policy issues, as well as implementation and dissemination. CAM modalities to be covered will include acupressure and mindfulness–based stress reduction with an emphasis on lessons learned from the laboratory and the clinic.

Biography:

Mark Kindy is Professor/Associate Chair for Research in the Department of Regenerative Medicine and Cell Biology at MUSC and Senior Research Career Scientist/Deputy ACOS for Research at the VA Medical Center in Charleston, SC. He received his BS from the University of Massachusetts in Zoology and PhD from Boston University School of Medicine in Biochemistry. He was a postdoctoral fellow at the Salk Institute. He was at University of Kentucky in the Department of Biochemistry and the Center on Aging. His area of expertise is neurodegenerative disorders, animal modeling, mechanisms associated with diseases and regeneration of the brain.

Abstract:

There are currently no effective therapeutic agents for traumatic brain injury (TBI), but drug treatments for TBI can be developed by validation of new drug targets and demonstration that compounds directed to such targets are efficacious in TBI animal models using a clinically relevant route of drug administration. The cysteine protease, cathepsin B, has been implicated in mediating TBI, but it has not been validated by gene knockout (KO) studies. Therefore, this investigation evaluated mice with deletion of the cathepsin B gene receiving controlled cortical impact TBI trauma. Results indicated that KO of the cathepsin B gene resulted in amelioration of TBI, shown by significant improvement in motor dysfunction, reduced brain lesion volume, greater neuronal density in brain, and lack of increased proapoptotic Bax levels. Notably, oral administration of the small-molecule cysteine protease inhibitor, E64d, immediately after TBI resulted in recovery of TBI-mediated motor dysfunction and reduced the increase in cathepsin B activity induced by TBI. E64d outcomes were as effective as cathepsin B gene deletion for improving TBI. E64d treatment was effective even when administered 8 h after injury, indicating a clinically plausible time period for acute therapeutic intervention. These data demonstrate that a cysteine protease inhibitor can be orally efficacious in a TBI animal model when administered at a clinically relevant time point post-trauma, and that E64d-mediated improvement of TBI is primarily the result of inhibition of cathepsin B activity. These results validate cathepsin B as a new TBI therapeutic target.

Biography:

David Allsop is Professor of Neuroscience at Lancaster University. He has been working on Alzheimer’s disease for around 30 years, and has published more than 120 papers on this and other neurodegenerative diseases. He is a member of the Research Executive Committee of The Alzheimer’s Society, UK.

Abstract:

Inhibition of Aβ oligomer formation could have a major impact on clinical progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). We are working on retro-inverso (RI) peptides and RI-peptides attached to the surface of nanoparticles as therapeutically useful inhibitors of early-stage Aβ aggregation. The inhibitor RI-OR2-TAT consists of the Aβ binding peptide RI OR2 (rGffvlkGr) attached to a retro-inverso version of the transit peptide ‘TAT’ to target the inhibitor into the brain. Fluorescein-RI OR2-TAT has been shown to cross the blood brain barrier (BBB) of APPswe/PS1ΔE9 transgenic mice and bind to β amyloid plaques. Moreover, daily peripheral injection of RI-OR2-TAT into these mice for 21 days resulted in a 25% reduction (p<0.01) of Aβ oligomer levels, a 32% reduction (p<0.0001) of amyloid plaque count, a 44% reduction (p<0.0001) in the numbers of activated microglial cells, and a 25% reduction (p<0.0001) in oxidative damage. Covalent attachment of RI OR2 TAT to liposomes, to produce peptide-inhibitor nanoparticles (PINPS), has resulted in a remarkably potent multivalent inhibitor that has several advantages over the free peptide for further development as a potential drug. These include biocompatibility, stealth properties (to avoid detection by the immune system) and the possibility of designing multi-ligand systems directed at more than one target. Various drug candidates aimed at inhibiting the formation of Aβ, or inducing the clearance of senile plaques from the brain, have failed in recent years. Our RI peptide and nanoparticle-based therapies are an alternative approach to more conventional drugs and could offer some hope for success in future human clinical trials.

Biography:

Chris Gamblin completed his PhD with Dr. Robley Williams, Jr. at Vanderbilt University and postdoctoral studies with Dr. Skip Binder at Northwestern University Feinberg School of Medicine. He is currently an Associate Professor in the Department of Molecular Biosciences at the University of Kansas and continues to investigate the biochemical mechanisms of tau aggregation.

Abstract:

The abnormal aggregation of the microtubule-associated protein tau is believed to result in cell death and cognitive deficits in Alzheimer’s disease and several other neurodegenerative diseases. The inhibition and reversal of tau aggregation would likely have therapeutic benefit for the treatment of such disorders. In our efforts to identify tau aggregation inhibitors (TAIs), we have sought to mine the secondary metabolome of the fungus Aspergillus nidulans for unique compounds with anti-aggregation properties. Fungal natural products have historically been a rich source of biologically important compounds ranging from anti-cholesterol medications to antibiotics. By screening just a small library of A. nidulans natural products, we were able to identify three lead compounds capable of inhibiting tau aggregation. One of these, asperbenzaldehyde, represented a novel class of TAI. Because asperbenzaldehyde is a precursor to the chemical class of azaphilones, we subsequently generated and analyzed the TAI activity of 11 azaphilone derivatives in vitro. We found that all azaphilone derivatives tested inhibited tau aggregation. Four of the compounds also caused the disassembly of pre-formed filaments in a dose-dependent fashion by reducing both the length and number of tau filaments. Tau also retained significant microtubule-stabilization activity even in the presence of the most potent TAI, indicating that the azaphilone scaffold may be a very promising structural core for future development of tau therapeutics.

Biography:

Rocco de Filippis completed his MD and PhD from Catholic University of the Sacred Heart in Rome. Investigator Meeting (Western Europe and North America) for BRENDA/pharmacological Study on Nalmefene (LUNDBECK - pharmaceutical company). Barcellona (Spagna) . He holds a Master’s degree and he improved respectively in Bipolar Disorders and Addictive behavior in the years 2011/2012. He currently works and at the Institute of Psychopathology - Rome as a Psychiatrist and Addictive Medicine, and up to now presented as scientific coordinator of CME and Master of Addictive Behaviors; he currently publishes on Bipolar Disorders with high specialization on rapid cycling;he is also an official candidate at the Psychoanalytic Italian Society of the First Italian Center of Rome, and member of IPSO (International Psychoanalytic Studies Organization). He had a oral speech at Translational Medicine 2014 in Las Vegas on QTc Prolungation and Psychotropic Drugs.

Abstract:

Objectives The study aimed to compare effectiveness and safety of short-term antidepressant treatment between patients with continuous (CCC) and non-continuous (N-CCC) cycling bipolar disorders. Methods The study sample included 101 patients with bipolar disorder, 22 (21.8%) CCC and 79 (78.2%) N-CCC. Response was defined as a HDRS21 total score <7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. Results Compared with N-CCC patients, CCC patients achieved a significantly lower percentage of response (respectively 50% vs. 82.3%, χ2=9.6, p=0.002) and remission (respectively 40.9% vs. 69.6%, χ2=6.11, p=0.013). Adjusted logistic regression analysis indicated that CCC patients were 4.3 times more likely to be non-responders and 3.3 times more likely to be non-remitters than N-CCC patients. Concerning AD safety, 1 (5.0%) CCC patient committed a suicide attempt and AD-emerging switch was observed in 2 patients with N-CCC (2.5%) and in 1 with CCC (4.5%). Limitations The observational nature of the study, retrospective assessment of course, and unblinded outcomes assessment. Conclusions Our findings indicate that the presence or absence of a free interval identifies two different forms of bipolar disorders with different response not only to prophylactic treatment, as previous reported, but also to short-term ADs. We submit that clinicians should take into consideration their patients\' pattern of cycling when prescribing short- term AD treatment. Moreover, subtypes of bipolar disorders might be used as moderators of treatment response in studies assessing the efficacy or the effectiveness of antidepressant treatment.

Biography:

I obtained a degree in Chemistry from Oxford, and a PhD in Biochemistry from London University. I acquired skills in protein science at UCLA in the 60’s, and an interest in brain peptides by working on endorphins at NIMR in the ‘70s. I started investigating the role of peptides and cellular protein mis-targeting in AD at St George’s in 1995, and found that raised cholesterol was a risk factor for -amyloid formation, and the small peptides were possible therapeutics.

Abstract:

-Amyloid peptides were isolated from plaques in post-mortem brains of Alzheimer’s patients some 40 years ago. Three types of evidence suggest they are causative in the cognitive loss of Alzheimer’s Disease (AD). (1) Mutations in the amyloid precursor gene (APP) and -secretase gene (PS1) responsible for its formation, are found in early-onset AD patients. These mutant gene expressed in transgenic mice give rise to memory defects. (2) The total amount of -amyloid in post-mortem brain correlates with the extent of cognition loss prior to death. (3) Aggregates of -amyloid proteins are toxic to neuronal cells in vitro and in vivo. In the last seven years, it has become clear that soluble oligomers of -amyloid block the synaptic plasticity required for memory formation and storage, whereas fibrils of insoluble -amyloid are relatively innocuous. Potential therapy against -amyloid has developed along two lines. First, vaccines against the peptide have been shown to clear amyloid plaques in patients, but have little effect on cognitive status. The suggestion is therefore, that therapy should be aimed at the formation of new oligomers of -amyloid, rather than clearance of mature fibril -amyloid in plaques. We have developed a number of retroinverted peptides that prevent formation of soluble amyloid oligomers, shown to prevent neurotoxicity to cells in culture. Some of these peptides have been converted into gadolinium-containing MRI contrast agents, and shown to be useful for -amyloid detection in the brains of 5xFAD transgenic mice.

Biography:

Distinguished Professor Ru-Band Lu graduated from National Defense Medical center Taipei, Taiwan, in 1972. He became a professor of Psychiatry at National Defense Medical Center in 1989. 1992 to 1993, he was a visiting scientist in Human Genetics at Yale University, New Haven, CT; he studied genetics, psycho-neuroimmune pharmacology. 2003 to 2009, he was the director of the Institute of Behavioral Medicine, National Cheng Kung University, Tainan, Taiwan. In this decade, he works in the developmental navel treatment model. He has published more than two hundred research articles in the recent fifteen years.

Abstract:

Low dose memantine might possess anti-inflammatory and neuroprotective effects mechanistically remote from the NMDA receptor. We investigated whether using valproic acid (VPA) add-on memantine (5 mg/day) to treat bipolar II disorder (BP-II) is more effective than using VPA alone. In this randomized, double-blind, controlled 12 week study, BP-II patients were randomly assigned to a group: VPA+Memantine or VPA+Placebo (Pbo). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response, alone with plasma levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), IL-8, and IL-1and metabolic profiles during week 0, 1, 2, 4, 8 and 12. After 12 weeks, there was a significant increase of high-density lipoprotein cholesterol (HDL-C) (p < 0.009) in the memantine group compared with the Pbo group. The TNF-α were significantly decreased in the memantine group than in the Pbo group (P = 0.013). The changes in HDRS score were significantly associated with changes in IL-6 (P = 0.012) and IL-1(P = 0.005) levels; changes in YMRS score associated with changes with TNF-α(P = 0.005) level changes. The association between BDNF Val66Met polymorphism with treatment response was evaluated. After stratified byBDNF Val66Met genotypes, significantly greater decreases in HDRS scores were found in the VPA+memantine group in patients with the Val/Met genotype (p=0.004). We conclude that memantine might benefit treatment of BP-II via decreasing cytokines and increasing HDL-C. The BDNF Val66Met polymorphism influences responses to add-on memantine by decreasing depressive symptoms in BP-II.

Biography:

Christopher J. Lahr is an associate professor in the departments of surgery, medicine and obstetrics and gynecology at the University of Mississippi Medical Center.

Abstract:

The vagus nerve ganglion inside the skull has an auricular branch (Arnold's nerve) that passes through Arnold's canal to enervate the sensory receptors in the inner surface of the inside of the concha of the external ear. If you stimulate Arnold's nerve you cause vagal stimulation. Arnold nerve stimulation via an earbud delivering electrical stimuli has been used in Europe to treat depression. It is possible that this electrical stimulation could be achieved with a simple smartphone app and acoustic earbuds. We have reviewed our experience with 54 patients diagnosed with gastroparesis into which we have placed gastrointestinal electrical stimulators then studied their results based upon Likert scale quantification of symptoms, neuronal cell counts of full thickness gastrointestinal biopsies, electrogastrographic evidence of GI electrical wave frequency and amplitude to personalize electrical stimulation by adjusting voltage (amplitude), frequency, pulse with and cycle times. 59% of patients showed immediate changes in electrical rhythm as well as symptomatic relief. Direct gastric electrical stimulation appears to have an effect on vagal mediated symptoms. This very preliminary data raises the possibility that direct vagal electrical stimulation (instead of indirect vagal stimulation via the gut) of the gut may have an impact upon other vagus mediated reflexes as well, such as its beneficial effect upon depression and epilepsy. Our current technique would use off the shelf devices to transcutaneously stimulate the vagus nerve or one of its branches to determine if such stimulation has an impact upon depression and epilepsy. The transcutaneous stimulation of the vagus nerve via its auricular branch would be achieved with a smartphone app with an internal safety valve. The heart rate is be regularly monitored and vagal stimulation stopped if the heart rate dropped below 60.

Biography:

John Kennedy is a pioneer in the field of Applied Neuroplasticity. He was contracted by the US Marines in 2006 to create a non-digital neuroplastic mental performance training program to reduce casualties in combat by improving attention, intuition and decision making under stress. He has since helped over 2500 people, in the areas of military, education, business, mental resiliency, improve their quality of life. He speaks regularly at corporate events and parent organizations on the topic of creating neuroplastically enriching environments. He is also the author of the forthcoming book Zombie Thinkingâ„¢- Why we do what we do and how to change it.

Abstract:

PACE is the core modality of Combat Brain Training™ (CBT) a unique, non-digital neuroplastic training regimen developed at the request of US Military forces to improve intuition and situational awareness. Vetted by USSOCOM, it has proven to be an effective pre-deployment force multiplier for all branches of the Armed Forces including Marines, SEALs, Snipers and Pilots. As Marines returned from combat with severe TBI, CBT was found to significantly accelerate recovery and is currently being integrated into Rush Hospital’s (Chicago) Road Home program for transitioning vets. It provides targeted robust mental stimulation to create long term potentiation in the areas of the brain associated with executive function using analog neuroplastic training tools. These changes solidify in as little as 20 minutes and after the stabilization process ends the synapse is significantly stronger - this process can occur as many times as need be until the synapse no longer receives the stimulation that is greater than it is prepared for, hence progressively accelerated cognitive exertion. The exercise tools look like games and can be performed with family and caregivers so sessions are fun and interactive and carry no stigma usually associated with interventions. In the civilian world it has helped victims of TBI from accidents, athletes suffering from concussions and children with severe LD. Over 2500 people have experienced PACE with 100% reporting significant improvements in real world performance

Biography:

Wayne Grant Carter received his Honors degree and PhD in Biochemistry from the University of Southampton, studying protein post-translational modification and molecular signalling cascades. He is currently a Group Leader in the School of Medicine, University of Nottingham, with research focused upon protein post-translational modification and molecular mechanisms of hepato- and neuro-toxicity.

Abstract:

The mechanism by which neurotoxicants, such as alcohol, damage neurons is not fully understood. To investigate the neuropathology arising from cumulative excessive alcohol consumption we examined prefrontal cortex brain tissue from human alcoholics and age, gender, and post-mortem delay matched control subjects. H&E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. One dimensional polyacrylamide gel electrophoresis proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. In alcoholics, significant loss of cytosolic α- and β-tubulins was also seen in the other brain regions examined: Caudate nucleus, hippocampus, and cerebellum. Collectively, our results suggest that the cytoskeletal architecture is notably susceptible to alcohol-related brain damage. Whether this represents a common pathological hallmark of neurotoxicants will be discussed.

Biography:

Sha Mi obtained her Ph.D. in Molecular and Cellular Biology from Rutgers University and her postdoctoral training in the laboratory of Dr. Richard Roberts (Nobel Laureate) at the Cold Spring Harbor Laboratory. Her major interests include the identification of novel CNS specific proteins involved in the regulation of neuronal cell survival, axonal regeneration, neuronal damage repair and remyelination. Her current focus is to identify therapeutics for the treatment of demyelination diseases such as MS. Her group is the first to identify proteins, LINGO-1 and DR6, that block remyelination repair in laboratory tissue culture and in animal disease models, and whose inhibition will allow for re-myelination and repair of damaged axons.

Abstract:

• LINGO-1 is a Leucine rich repeat, Ig domain containing, Nogo receptor interactive protein that is selectively expressed in CNS oligodendrocytes and neurons. Its expression is developmentally regulated, as well as up-regulated in CNS diseases and spinal cord injury. LINGO-1 negatively regulates oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration by activating RhoA and inhibiting ATK phosphorylation. Across diverse animal CNS disease models, targeted LINGO-1 inhibition promotes neuron and oligodendrocyte survival, axon regeneration, oligodendrocyte differentiation, remyelination and functional recovery. The targeted inhibition of LINGO-1 therefore represents a novel approach for the treatment of neurological diseases. BIIB033 is the first anti-LINGO-1 anti-body to enter clinical development for CNS repair. The Phase I study found anti-LINGO-1 to be safe and well tolerated up to the maximum planned dose of 100mg/kg. BIIB033 is currently being evaluated in Phase II clinical study for the treatment of RRMS and SPMS

Biography:

Bekker is an internationally recognized expert in neuroanesthesia and is frequently invited to speak at Grand Rounds and Scientific Panels. Dr. Bekker has been active in research for many years. He is the author of 62 peer reviewed publications, 6 US patents, 32 educational reviews and more than 100 abstracts. His work has focused on perioperative brain protection, neuroinflammation, and clinical pharmacology. Dr Bekker was a PI of numerous clinical trials, including studies sponsored by the National Institute of Aging. He serves on the editorial board of the Journal of Neurosurgical Anesthesiology and is an ad hoc reviewer for 15 peer-reviewed journals, including NEJM, Anesthesiology, Neurosurgery, and Anesthesia and Analgesia. Currently, Dr Bekker is spearheading a campaign to improve the efficiency of Perioperative Services as well as Patient Safety at the University Hospital

Abstract:

The brain is vulnerable during the perioperative period. Neurobehavioral disturbances are common complications of surgery, manifesting in three distinct forma: emergence delirium, postoperative delirium, and POCD. The relationship between these conditions has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric population. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD is a condition characterized by deterioration of cognitive performance after surgery presenting as impaired memory and/or concentration. Perioperative physiological derangements (e.g. hypotension), anesthetics, duration of surgery, respiratory complications have been suggested as possible causes, but only age and limited education has proven to be consistent risk factors in most studies. Current research suggests that patients with preoperative cognitive impairment are at higher risk for POCD because of their already compromised status and their potential vulnerability to worsen into dementia due to a less cognitive reserve. In this presentation, we review the definitions, etiology, prevention and treatment of both disorders in patients undergoing major non-cardiac surgery.

Biography:

Naseer nadim completed his MD in 1982 from Sackler School of Medicine, Tel-Aviv. Previously he was working as Paediatric Residency & specialty at Porya Hospital, Tiberias, Rambam and Naharya HospitalS successively. Currently he is conducting a research on Periodic Fever at Clalit Health ORG. He is an honourable member of the European Society of Pediatric Cardiology and the Israeli Heart society

Abstract:

There is a considerable impression that the clinical descriptions of diseases of the white matter still suffers from vagueness and lacks organization, thus leaving the diagnosis of these disorders yet in a state of uncertainty. It is possible that the reason for opacity of these diseases is the widespread distribution of white matter through the body; from cerebrum till the nerve fibers endings in periphery; making the description of their injury symptoms and signs, despite being true, to be burdened by a list of scattered different details in a non-systematic manner, and lacking a pathognomonic sign, or a combination of signs, that could direct the clinician to diagnose a specific myelination disorder. Though, the distinction between central and peripheral nervous system disorders has been well established, by the finding of hyperreflexia in the former and areflexia in the later. The recently published; “MAIS-NADIM NASSER triad”, or (MNN triad), is a simple, but solid marker, based upon injury to three brain organs; first, the white matter in the brain’s sub-cortical sites, second the brainstem, and third are the optic nerves and tracts. It is assumed that a mutational myelination disorder of the central nervous system usually hits all the above mentioned three sites at the same time, or sometimes sequentially, sometimes after long periods between one and the other; thus causing the appearance of three major signs in the same order of the injuries occurrence. Based on the above information one can conclude that clinicians should follow up patients who suffer from one single sign; truncal hypotonia, for example, or sensorineural deafness, or nystagmus, and wait for the appearance of the two other signs of the MNN triad, so LD diagnosis at hand.

Biography:

Benjamin Van Voorhees, MD, MPH, is currently an Assistant Professor and the Interim Head of the Department of Pediatrics at the University of Illinois at Chicago Children’s Hospital. He received his BA in History from Dartmouth College, his Doctor of Medicine from Vanderbilt University, and his Master of Public Health from Johns Hopkins. He completed a Combined Internal Medicine-Pediatrics Residency at Vanderbilt University Hospital and a General Internal Medicine Fellowship at Johns Hopkins. He has received several grants ongoing research support (RDJF, NIMH, NARSAD, CMS, and CDC since 2002)—two will take special notice: (1) From NIH he has an R01 for Primary Care Internet-Based Depression Prevention for Adolescents (CATCH-IT) from 1/15/11-5/31/16. This a randomized clinical trial to determine if a primary care internet-based depression prevention intervention (CATCH-IT 2R) can build resiliency and protect adolescents (ages 13-17) against depression and strengthen their ability to attain their life goals. In 2014 his CMS grant, University of Illinois CHECK (Coordination of HEalthcare for Complex Kids) grant from 09/01/2014 - 08/31/2017 received total funding of $19,581,403. CHECK seeks to provide comprehensive, highly-innovative community-based care to 6000 children and young adults enrolled in Medicaid in Cook County, Illinois. CHECK is designed to improve care for populations with specialized needs, with a focus on the specific priority area of high-cost pediatric and young adult populations.

Abstract:

Efforts to prevent depression have become a key health system priority. Currently, there is a high prevalence of depression among adolescents, and treatment has become costly due to the recurrence patterns of the illness, impairment among patients, and the complex factors needed for a treatment to be effective. Primary care may be the optimal location to identify those at risk by offering an internet-based preventive intervention to reduce costs and improve outcomes. Few practical interventions have been developed. The models for Internet intervention development that have been put forward focus primarily on the Internet component rather than how the program fits within a broader context. This paper describes the conceptualization for developing technology based preventive models for primary care by integrating the components within a behavioral vaccine framework. CATCH-IT (Competent Adulthood Transition with Cognitive-behavioral, Humanistic and Interpersonal Training) has been developed and successfully implemented within various health systems over a period of 14 years among adolescents and young adults ages 13-24. We describe more than a decade of technology development, clinical trials and investigations into mechanisms of action for this “technology based behavioral vaccines”.

Biography:

Priscilla Chukwueke obtained her medical degree from American International School of Medicine, Guyana, South America, and has a Master’s degree in public health. She is currently pursuing her psychiatry residency at Harlem Hospital /Columbia University in New York, USA. This case report was done in conjunction with a neurologist- Dr. Anne Kleiman and a radiologist- Dr Leszek Pisinski all from Harlem Hospital / Columbia University and it has been published in clinical Neuropsychiatry journal in June 2015. She has presented posters nationally and internationally e.g. at The World psychiatric Congress in Madrid Spain in 2014.

Abstract:

Marchiafava-Bignami Disease (MBD) is a rare central nervous system (CNS) disease characterized by demyelination of the corpus callosum. It is mostly found in men with alcohol use disorder and malnutrition with cases reported worldwide across all races. The onset of the disease may be sudden presenting with stupor, coma or seizures while some may present with gait abnormality (spasticity), psychiatric problems, hemiparesis, aphasia, apraxia and incontinence with a resultant high morbidity and mortality rates. Case description: patient is a 30 year old left handed African-American, who presented with c/o altered mental status, urinary incontinence, slurred speech and left-sided weakness. The diagnosis of MBD was confirmed with DTI Tractography which showed significantly Diminished commissural fibers extending to the right central semiovale lesion, near absent or significantly diminished commissural fiber extending through the corpus callosum indicating demyelination. Discussion: MBD is often an incidental diagnosis with high morbidity and mortality. This is different from previous casas because of earlier onset as opposed to onset around age 45, rapid recovery and minimal disability as he could walk independently before discharge from hospital. This case also shows added benefit of the DTI tractography in the diagnosis of MBD.

Biography:

Abstract:

Biography:

Robert Michael Davidson completed his PhD in Pharmaceutical Chemistry at the age of 26 from UCSF, NSF postdoctoral fellowship at the National Bureau of Standards, Center for Analytical Chemistry, MD degree at St Louis University School of Medicine, Nuclear Medicine residency at Baylor College of Medicine, Houston, Texas, and Internal Medicine residency in Phoenix, Arizona. He was Associate Medical Director for DuPont Pharma’s Radiopharmaceutical Division1990-1992. He has published more than 30 papers in peer-reviewed journals. He is a Fellow of The American Institute of Stress (2012-present) and practiced complementary, alternative, integrative internal medicine in Gladewater, Texas (2008 – 2015), for PhyNet Inc.

Abstract:

A new hypothesis as to the organizational basis of cells, organism, and nervous system - the “fractal dimension” - is presented. Alteration in biological water dynamics likely precedes the onset of inflammation, maternal immune activation, and IL-6 elevations, in autism. Exogenous interfacial water stress (EIWS) leads to concomitant disruption of multiple biosemiotic levels, including the heretofore, seldom considered sub-atomic level, i.e. that of the hydrated electron. Biological water at the interphase of proteins in the CNS is self-ordering, fractal, and birefringent. DTI-MRI studies of the brain show loss of fractional anisotropy prior to overt manifestations of brain disorders, including autism. Recent description of “fractones” in the basement membranes of hippocampal subventricular zones of the brainstem is perhaps not by serendipity, the same general location in which several neurotropic viruses and neurotoxicant metal aquo cations, i.e. Al3+, are sequestered. Fractones have been proposed as the organizing features of the HSPGs in the ECM of the CNS and throughout the human body, including the heart, gut, and bone marrow. We propose that the origin of the “fractal dimension” is not that of polyLM, but instead has a subatomic basis, originating from the hydrated electron. While the definitive structure of hydrated electrons is still being explored scientifically, present data has shown it to consist of cyclic hexamers of water, surounding or dispersing the negatively-charged electron density. We proposed a cyclic mesomeric hexameric bipolaron in 2013, as a putative molecular basis for proton-coupled electron transfer. The hydrated electron gives rise to the fractal dimension.

Biography:

Marion Schneider has completed his PhD with honors at the age of 26 years from the University of Bonn, Germany and postdoctoral studies from Institute Pasteur, Paris, France. She finalized her habilitation in 1988 on Immunology and teaches in Immunology in a variety of inflammatory diseases including SIRS, sepsis and neuroinflammation. She leads the Section on Experimental Anesthesiology in Ulm, Germany since 1997. She published more than 250 original manuscripts and provides ample experience on biomarkers in various diseases and signaling. Her current focus are in vivo activated antigen presenting cells.

Abstract:

Inflammatory antigen presenting cells (APC, dendritic cells and macrophages) are characteristic for patients with affective disorders and can be enriched from Ficoll-isolated mononuclear cells by 3-4 weeks of in-vitro culture. Flow cytometry, electron microscopy, Western Blots and cytokine quantification were applied to characterize the cell type and the inflammatory response in blood and cerebrospinal fluid (CSF). These analyses demonstrate that the enriched APC can be classified into either dendritic cells (iDCs), M1 or M2 macrophages. All cell isolates display high macropinocytotic activity and in addition form prominent autophagous vacuoles. The M1 type occurred more often in affective disorders than in schizophrenics. M1 cells expressed the ATP-sensitive P2R7 ion channel. ATP stimulation of the P2X7 ion channel caused the release of plasma membrane vesicles and microparticles (MP). MPs enriched from blood-derived APC cultures and from native CSF were subjected to protein chemical as well as miRNA analysis. All MP preparations were β-actin positive and in part stained for the autophagy marker LC3-II. When compared to the cultured APC-target cells, the microparticles were stronger positive for arginase 1, CD95, S100 and CD178, whereas CD36, and the TNF-R type I (CD120a) were decreased. MiRNA analysis revealed inflammatory signatures in the majority of affective disorders. These results indicate that microparticles may transport protein and miRNA species to target tissues. The current protocol proved to be valid to simultaneously study MP generation in vitro using cultured APC and to isolate and characterize MP from the CSF.

Biography:

Hans-Ulrich Demuth has completed his PhD at the age of 28 and his doctorate of sciences at the age of 36 years from Martin-Luther-University, Halle/S., Germany. He did postdoctoral studies at University of Kansas and the Uppsala Biomedical Research Center. He has inaugurated and co-founded Probiodrug in 1997, the company which has developed the concept of inhibition of Dipeptidylpeptidase-4 as treatment of type-2 diabetes (on the market since 2006). He has published more than 300 papers in reputed journals and has been serving as an editorial board member and reviewer of repute. In 2013 he founded the Fraunhofer-IZI department MWT.

Abstract:

Alzheimer’s disease (AD) is characterized by neuron-loss and neuro-inflammation. Although N-truncated and N-pyroglutamated Aβ-peptides (pGluAβ) are known as prominent constituents of plaques in AD-brain, their importance was overseen and pathways leading to their formation not understood. Because of their abundance, resistance to proteolysis, such N-terminally modified peptides can be important for initiation of pathological cascades leading to AD. Our work uncovers, that N-terminal pGluAβ-formation is catalyzed by QC1. QC-expression is upregulated in the cortex of individuals with AD and correlated with the appearance of pGlu-modified Aβ. Oral application of QC-inhibitors resulted in reduced pGlu3Aβ42 burden, but surprisingly also to the attenuation of the 1.000fold higher amounts of total Aβ in transgenic AD-models1. These observations led to the hypothesis that pGluAβ can seed Aβ-oligomerization by self- and co-aggregation with other monomeric Aβ-species2. Amounts of less than 10nM pGlu3Aβ42 generated cytotoxic oligomers which are over 20 fold more stable than oligomers of “classical” full-length Aβ-peptides. Such mixed pGlu3Aβ42-oligomers propagate their toxic structure in a prion-like manner. Moreover, the neurotoxicity unfolds to be tau-dependent in cell culture as well as in animal models. There, specific neuronal expression of pGluAβ provides in vivo evidence for profound pGluAβ neurotoxicity and gliosis induction2. Hence, a drug development program was entering regulatory testing 2010. Two phase 1: Single (SAD) and multiple ascending dose (MAD) trials of the compound PQ912 in healthy volunteers were conducted. They revealed PQ912 safe and well tolerated. Dose-proportional pharmacokinetics and a strong pharmacodynamic relationship were observed in plasma and CSF justifying studies involving patients. PQ912 is the first QC-inhibitor for treatment of AD since March 2015 in phase 2. Our research concentrates further on posttranslational modifications of Aβ leading to alternative pathways of the turnover of precursor protein APP.

Biography:

Carmeli is an Associate Professor in the Physical Therapy Department at Haifa University. He is the chairperson of the Master Degree program in the university. He served for six years as the Chief Editor of the \"Israeli Physiotherapy Journal\". His main research and teachings areas are Physical Function at advanced age, and biology of skeletal muscle.

Abstract:

Enhancement of motor performance is crucial in rehabilitation after a stroke. A new concept in motor learning and rehabilitation is error augmentation: using erroneous sensory feedback to enhance adaptation to a new environment. However, the clinical efficacy of this method to enhance motor learning after a stroke needs to be evaluated. To determine the efficiency of Error-Augmentation therapy over sham robotic training for the enhancement of the upper extremity motor performance after a stroke. Ten patients after a stroke randomly assigned into study or control groups. The study group (EA) executed error-augmentation training using DeXtreme robotic interface with the activation of a force field, while the control group (Cont.) executed a robotic training using the same devise, without the activation of the force field. Both groups carried out 12 treatment sessions by the same protocol. The effect of treatment was measured by the robotic devise by two objective outcomes: 1) Mean trajectory error; 2) Total performance score in hand reaching. The study group (2802 ± 473) and the control group (1160 ±1155) displayed an increase in total performance score, and reduction in mean error (6.2 ± 5.5 and 2.2 ± 4.5 respectively), in four weeks of error-augmentation treatment for the upper extremity. Error augmentation training implemented by robotic interface has been shown to potentially be an efficient platform to enhance upper extremity motor performance after a stroke.

Biography:

Makarenko O.M. has taken PhD degree at the age of 30 at the Moscow medical stomatological institute, M.D. degree at the age of 40 at the Institute of higher nervous activity in Moscow. He carries out his post-dock researches at the Institute of higher nervous activity and T. G. Shevchenko national university of Kiev. He is a professor of the psychology department, the author of more than 100 articles in reputed journals and 4 monographs (Lambert Academic Publishing).

Abstract:

Trophinotropins (TT) or neurotrophinotropic growth factors (NGF) are the group of endogenous therapeutic factors, which are actively secreted by cells of the organism being in the state of restoration after pathological process modeling or under recovery/remission. A distinctive feature of TT action is the activating influence on the cells of damaged tissues and organs along with their protective and immune-corrective mechanisms of action. «Cerebral» is the agent separated from nerve cells of the cerebral cortex of pigs, experienced bihemispheric autohemorrhagic stroke. It contains a complex of low-molecular pharmacologically active peptides (less than 1200 Da). The drug is characterized by its cerebrotropic multimodal action on nerve cells, which main effect is a trigger trophinotropic regulatory action on secretion of NGF and other cytokines. «Cerebral»’s application increases the level of synthesis and secretion of NGF in the conditions of experimental hemorrhagic stroke and at the same time does not influence synthesis and secretion of this growth factor in the intact animals. In the experiment, NGF secretion in the CNS was increased under intranasal way of introduction because the concentration of mRNA NGF was 0,05-0,74 pmol/l on the 2nd day after introduction (whereas concentration under intraperitoneal introduction was 0,05-0,10 pmol/l mRNA on the 2nd day) at the expense of express delivery of its molecules into the brain. The drug showed neuro-activating action in acute and remote from the beginning of stroke deseases periods, modifies cellular metabolism, restores unconditional reflex reactions and lost functions, activates the process of intellectual and psychoemotional activity.

Biography:

After his BSc Honours and an MSc in theoretical mathematics, Professor Toro obtained a PhD in computational mathematics applied to fluid dynamics. Since then, much of his research has been centred on the numerical analysis of partial differential equations and aerospace, industrial, environmental and medical applications. He is author of almost 300 works and has received several awards, including two honorary doctorates and the honorary title OBE from her majesty The Queen Elizabeth II. Prof. Toro’s current research is focused on the bio-physics of neurological diseases and their potential link to venous haemodynamics and transport across the blood vessel wall

Abstract:

Recent medical research has identified a strong association between some pathologies of the central nervous system and anomalous cerebral venous haemodynamics. Such pathologies include Retinal Abnormalities, Transient Global Amnesia, Transient Monocular Blindness, Meniere’s Disease and Idiopathic Parkinson\'s Disease. Here we focus our attention on the biophysics of the circulation to address some of the questions raised regarding some of these brain pathologies, one of them being the hypothesis of brain venous hypertension. Such hypothesis is difficult, if not impossible, to prove through direct invasive measuring methods. Here we adopt a theoretical approach to study the problem, through a mathematical model for the full human circulation [1], [2], [3]. The model includes sub-­‐models for the arterial system, the microvasculature, the venous system, the heart and the pulmonary circulation. The model adopts a geometric multi-­‐scale approach comprising 1D models for major vessels and 0D models for the remaining components. Particular attention is paid to the brain venous system, allowing for the use of MRI-­‐acquired patient specific geometries and adopting a refined representation of the cerebral venous network, including models for the Starling-­‐like behaviour of cerebral veins and admitting the interaction of the blood with the cerebro spinal fluid. The model has been validated by using available data in the literature and specially obtained in vivo MRI cerebral flow quantification data. In this paper we apply our mathematical model to demonstrate that extra-­‐cranial venous strictures, such as malfunctioning valves and stenosis, cause intracranial venous hypertension. We show results of relevance to Meniere’s Disease, Idiopathic Parkinson\'s Disease and Multiple Sclerosis. We speculate on the potential clinical implications.

Biography:

Jan Hemza is currently working at Brno Epilepsy Centre at the Department of Neurosurgery at the Masaryk University

Abstract:

Our study about new physiological quality of vessels (angiosynizesis, self-excitation all vessel vibration), the movement of brain and flow of cerebrosinal fluid (effect of movement and exachanges during time of verbral column, especially 3D exchanges vertebral column canal) together go to realisation that the pulsing flow in live organism is essential. All study have similar design: experimental study, mathematical models, experimental models. Pulsing flow isn´t, e.g. the problem nonpulsing flow at arteficial pump in blood circulation, during time delay ischemic tissue deposit will be developed. The vibration of vessel wall during physiological state, facility begining of angiosynizesis by propagation pulsing pressure wave, structural stability of bridging veins can be restore by adequate rise in pressure in given moment. Pulsing system have a more side effects, maybe to electromagnetic continuum into live organism on remodeling live organism during life and on thermodynamic dissipation. The venous brain system has active and regulatory function in hemodynamic flow of brain

Biography:

Nan-Shan Chan completed his Ph.D on Immunology in 1984 from Medical University of South Carolina and currently he is an acting Director for the Institute of Molecular Medicine in the College of Medicine at National Cheng Kung University where his research is focused on elucidating the functional interactions between cancer cells and the innate immune system. How cancer cells evade immune attack and prevent death-inducing factors-initiated apoptosis has been our focus of research. To understand how cancer cells develop resistance to tumor necrosis factor (TNF), we have utilized functional cloning and microarray approaches to isolate genes, which may regulate cancer cell sensitivity to toxic cytokines. We have recently discovered a tumor suppressor WOX1 (also named WWOX or FOR), which enhances TNF function and is apparently involved in embryonic cell differentiation and cancer pathogenesis.

Abstract:

Substantial evidence reveals that tumor suppressor WW domain-containing oxidoreductase (known as WWOX, FOR or WOX1) blocks the progression of Alzheimer’s disease (AD). We have first demonstrated that WWOX binds tau and tau-hyperphosphorylating enzymes GSK3, ERK and JNK1, and thereby inhibits tau hyperphosphorylation (JBC 279:30498, 2004; Cell Death Differ 19:1049, 2012). In addition, WWOX promotes neuronal differentiation. Unfortunately, WWOX is frequently downregulated in the AD hippocampi (JBC 279:30498, 2004). And, this downregulation results in spontaneous aggregation of TIAF1 and TRAPPC6A, which leads to caspase activation, tau aggregation, APP degradation, formation of amyloid  and plaques in humans and in Wwox gene knockout mice (Cell Death Dis 1:e110, 2010; Oncotarget 6:3578, 2015). When WWOX protein is lost due to alteration of WWOX/Wwox gene such as missense or nonsense mutation and deletion, this leads to ataxia, epilepsy, dementia, neurodegeneration, diseases associated with HDL lipid metabolism, and early death in humans, mice and rats (Oncotarget 5:11792, 2014; Exp Biol Med 240:400, 2015). Our studies revealed that significant upregulation of proteins, which are involved in neurodegeneration, is found in the cortex and hippocampus of Wwox gene knockout mice. These proteins include GSK3, ERK, pERK, JNK1, pJNK1, TIAF1, pS35-TIAF1, TRAPPC6A, pS37-TRAPPC6A, -synuclein, C9orf72, TDP-43 and others. Notably, a zinc finger-like peptide Zfra is able to ameliorate the symptoms of AD in the triple transgenic mice, including neuronal death and memory and learning capabilities, suggesting its potential use in therapy for AD. (supported by DoD, USA and MOST and NHRI, Taiwan)

Biography:

Michele Mishto is a postdoc since 2005. He is currently working in the group of Peter Kloetzel (Institut für Biochemie, Charité Berlin). His main interests are proteasome isoforms functions with outcomes on: (i) neuroinflammation and its involvement in neurological diseases such as AD, MS and epilepsy; (ii) tumors; (iii) antigen presentation and immune response. He has 31 publications in peer-reviewed international journals (15 as first or last author) and H-index = 16.

Abstract:

The proteasome is the core of the ubiquitin proteasome system and is involved in several cellular metabolisms. The incorporation of three inducible immuno-subunits into the proteasome results in the generation of the so-called immunoproteasome, which is endowed of pathophysiological functions related to immunity and inflammation. We have shown that immunoproteasome is almost absent in healthy human brain, while it is induced in the patients affected by Alzheimer disease (AD), multiple sclerosis (MS) and temporal lobe epilepsy (TLE). The expression of immunoproteasome in the brain can affect the microglia activity in AD model, the neuronal activity in TLE animal models and the presentation of myelin antigens involved in MS. Immunoproteasome can affect the neuroinflammation by acting not only as intracellular but also as extracellular protease. Indeed, we show that extracellular proteasome seems to be involved in the regulation of the pleiotropic cytokine osteopontin, thereby playing a role in the development of relapse in RRMS patients. Recent studies on animal models identified immunoproteasome subunits as potential targets for treatment of MS and pharmaco-resistant epilepsy forms.

Biography:

Kuna Yellamma has completed her graduation from Sri Satya Sai Arts & Science College for Women, Anantapur during 1972-75 and Post Graduation in 1977 from S.V.University, Tirupati. She was the recipient of Prof. I.M. Rao Prize for obtaining First Rank in Botany in B.Sc.; secured Second Rank in Zoology in B.Sc. (1975), S. V. University, Tirupati; Fourth Rank in M.Sc. Zoology, S.V.University; Best Speakers prize at seminar in M.Sc. (1977); Commonwealth Academic Staff Fellowship, UK. (1993); S.V.University, Meritorious Women Teacher award-(2000); NTR Mahila Puraskar from Andhra Pradesh State Government, (2001); Honorary Appointment to “The Research Board of Advisors” by American Biographical Institute, USA, (2001-to todate); Nominated for women of the year Award – 2005 by ABI, USA; Shiksha Rattan Puraskar with certificate of Excellence by India International Friendship Society, Bangalore- (2007): S.V.U.Teacher of Excellence Award-2009; NESA Fellowship Award-2010; IAO Certified Faculty Member from International Accreditation Organization, USA– 2012.

Abstract:

Alzheimer\'s disease (AD) is a neurodegenerative disorder mainly occurs in the older people. The pathological hallmark of AD is characterized by the progressive loss of basal forebrain cholinergic neurons that innervate the hippocampus and cortex. Accumulation of extracellular of amyloid-β and intracellular tau protein in brain leads to cognitive impairments. In the present study the rats were injected (I.P.) with D-galactose (D-gal) for 6 consecutive weeks to induced AD characters. The experimental rats were subjected to Morphometric, Learning & Memory efficiency by using Morri water maze test and to investigate neuroprotective activity of the silk Protein, Sericin on Alzheimer’s induced rat. The rats were orally treated with extracted silk protein, Sericin from B. Mori., cocoons. The biochemical changes in Ach and AChE level and Histological pathological changes were observed in selected brain regions. The results of Morphometric, Learning and Memory efficiency, Ach and AChE level and Histological changes revealed that Sericin could reverse the D-Gal induced AD damage in neurons of Cortex and Hippocampus regions and enhances the Learning and Memory efficiency in AD induced rats. From all these findings, it was finally concluded that, Silk Protein, Sericin may be use as a potential cognitive to treat Alzheimer’s Disease.

Biography:

Jack Rogers, PhD. is a Leading authority on the role of RNA in the maintenance of iron homeostasis related to disease processes in the blood (anemia) and in Alzheimer’s disease, and more recently in the etiology of Parkinson’s disease. Director of the Neurochemistry Laboratory in the Psychiatry Department at Massachusetts General Hospital and at the Harvard Medical School, Jack has an extensive funded track record in established scientific journals (Cell, J. Biol. Chem. including cover issue). His peer-reviewed publications won him a Zenith award from the Alzheimer’s Association on the subjects of iron metabolism, and translational control in Neurodegenerative diseases.

Abstract:

Manganese (Mn2+) is an essential trace element although occupational over-exposure to manganese has been linked to a neurodegenerative disease, termed Manganism that is uniquely related, but distinct from Parkinson’s disease. We demonstrated that Mn2+ dose-dependently inhibited translation of both the iron storage protein ferritin and iron-export amyloid precursor protein (APP), each as central iron homeostatic proteins that promote neuroprotective cellular survival in SH-SY5Y neuronal cells, rat brain, and in Parkinson’s disease brain tissue. This action was manifested via iron-responsive element (IRE) sequences in the 5’untranslated region (5’UTR) of the APP transcript. Levels of iron-regulatory protein-2 (IRP-2) translational repressor were decreased in response to Mn2+ influx suggesting that only sufficient levels of IRP1 remained and were therefore critical in the pathway of Mn2+ inhibition of both ferritin and APP translation. Consistently, Mn2+ toxicity was only modestly evident in cells up to 24 hours of exposure, even when these cells progressively exhibited total shut down of the ferritin /APP expression at the level of message translation. In this regard, the consequences of the loss of the protective axis of APP and ferritin expression against iron catalyzed oxidative stress became clear after 24 hours when we observed a consistent and timed dramatic fall in cell viability after 48 hours and 72 hours metal exposure. We conclude the Mn2+ toxicity is partly attributable to translational inhibition pathways operating on APP and ferritin such that their absence embargoes neuroprotective iron export and storage to increase neurotoxic reactive oxygen species (ROS) in these cells, with subsequent and rapid neurotoxicity.