Day 3 :
- Neurological disorders
Blood Brain Barrier and Diseases
Neuroimmunological Infectious Diseases
University of California, USA
Title: Impact of Bone Fracture on Stroke Recovery
Time : 09:30-09:50
Hua Su, MD, is Professor and the Associate Director of Basic Science Research at the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care at the University of California, San Francisco. Dr. Su is an experienced vascular biologist. Her long-term research interest is to develop therapeutic strategies that can improve outcomes in patients with vascular disease. Her current research projects are (1) Cerebrovascular malformation modeling, mechanistic study and new therapy development, and (2) Impact of peripheral injury on stroke recovery. Dr. Su was born in China, where she obtained her degree in Medicine in 1982. In 1989, she undertook a Postdoctoral Research Fellowship at University of California, San Francisco. She joined the faculty at University of California, San Francisco in 1996 and led a group developing gene based therapies for cancer, myocardial infarction and ischemic limb diseases. She was recruited to the Center for Cerebrovascular Research in 2008. Since then, her research was focused on identifying disease mechanisms and developing new therapies for cerebrovascular diseases and ischemic stroke.
Stroke is the leading cause of disability in adults and an important risk factor for bone fracture. Alternatively, stroke is one of the most devastating complications of bone fracture. In the United States, approximately 70,000 stroke victims suffer from bone fracture within the first year after their stroke. Reported date showed that about 0.2% to 4.1% patients suffer from stroke after hip surgery. However, the impact of bone fracture on stroke recovery has not been fully studies. We have studied the influence of bone fracture shortly before or after ischemic stroke on stroke recovery in a mouse model. We found that bone fracture increases alarmins and pro-inflammatory cytokines in the blood and increase stroke related injury as well as functional deficits through augmenting the neuroinflammatory response. Mice with stroke and bone fracture have more severe functional deficits, larger infarct sizes, and more CD68+ macrophages in the peri-infarct region than mice that have stroke only. Bone fracture also increases oxidative stress in the injury and promotes pro-inflammatory polarization (M1) of macrophage. Anti-inflammatory therapies reduce the negative impact of bone fracture on stroke recovery. In a clinical study, we found hip fracture patients with advance age are prone to have ischemic stroke and higher CHADS2 score and neutrophil counts are risk factors for post-fracture ischemic stroke. Prior bone fracture history is an independent risk factor for ischemic stroke. These findings could help doctors identifying fracture patients that at risk of post-fracture stroke and providing preventive therapies to these patients before surgical fixation.
University of Surrey, UK
Title: Targeting soluble oligomers associated with Alzheimer with antibody-secreting mesenchymal stem cells
Time : 09:50-10:10
Mourad Tayebi was awarded a PhD in Neuroimmunology from Imperial College. He worked as Senior Research Fellow at the University of Sydney before returning to the UK and accepting an academic position at the Royal Veterinary College leading a team of scientists with a specific focus on protein misfolding diseases. He was offered a Faculty position at UT Health where he led a team of scientists interested in investigating the molecular mechanisms underlying protein misfolding/aggregation. His research focuses on refining the therapeutic strategies through developing novel antibodies that would specifically recognize the oligomeric forms of misfolded proteins. His team developed a panel of camelid antibodies able to transmigrate across the blood-brain barrier and enter the cell membrane of neurons.
Although there is currently no effective treatment for Alzheimer’s disease (AD), significant advances have been made in suppressing its progress, using conventional antibodies that block aggregation of the abnormally folded proteins. The major limitation in targeting plaques and aggregates associated with Alzheimer in the CNS is the blood-brain barrier (BBB), which restricts the access of biologics and drugs to the brain parenchyma. To that end, we used anti-oligomer PRIOC-antibody-secreting mesenchymal stem cells (MSCs) modified by Zinc Finger Nuclease (ZFN) technology. Tg2576 and htau mice models were used to assess the therapeutic efficacy of a sustained local delivery of PRIOC mAbs in situ. This led to substantial reduction of Aβ plaques and aggregate formation/reduction and neuropathology and improvement of cognitive deficits in these animals. Our preliminary results indicate that this strategy might be useful in reducing Aβ burden and neuropathology recognized in Alzheimer patients.
Robert S. Fujinami
University of Utah School of Medicine, USA
Title: DA virus mutant H101 can alter t cell mediated cns pathogenesis through virus induced immunosuppression
Time : 10:25-10:50
Robert S. Fujinami completed his PhD from Northwestern University and postdoctoral studies from the Scripps Research Institute. He is a Professor in the Department of Pathology at the University of Utah. He was the first recipient of the Harry Weaver Award from the National Multiple Sclerosis Society and he is a Jacob Javits Neuroscience recipient from NINDS, NIH. He has published more than 200 articles and has been serving as member on various editorial boards and NIH review panels.
Viruses have immunomodulatory properties for the purpose of evading clearance by the host. We are investigating how a few changes in the Theiler’s murine encephalomyelitis virus (TMEV) genome could provide a means to suppress T cell mediated central nervous system (CNS) disease. The mutant TMEV virus, H101, in its natural host (the mouse), causes immunomodulation when administered via a peripheral route (intraperitoneal – i.p.). In contrast, C57BL/6 mice infected with the wild-type DA strain of TMEV via the i.p. route develop an asymptomatic infection and clear the virus. C57BL/6 mice infected with the H101 mutant virus via the i.p. route become immunosuppressed through the depletion of T cells. Intracerebral infection of C57BL/6 mice with lymphocytic choreomeningitis virus (LCMV) leads to death around day 6 post infection due to an aggressive anti-viral CD8+ T cell response. Infection of mice with H101 prior to infection with LCMV results in a majority of mice surviving past day 7 post-LCMV-infection. Similarly, infection, with H101, of mice with relapsing-remitting experimental autoimmune encephalomyelitis results in elimination of the CD4+ T cell mediated disease exacerbations. This study provides experimental evidence that viruses can be used to treat T cell mediated CNS disease.
Stephen D. Miller
Northwestern University, USA
Title: Therapeutic Infl ammatory Monocyte Modulation using MARCO-Targeting Carboxylated Immune- Modifying Nanoparticles for Amelioration of Neuroinfl ammatory Disease
Time : 10:45-11:05
Stephen Miller is the Judy E. Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine in Chicago. He received his Ph.D. in 1975 from the Pennsylvania State University and did postdoctoral training in cellular immunology at the University of Colorado Health Sciences Center before joining the faculty at Northwestern in 1981 where he currently serves as Director of the Northwestern University Interdepartmental Immunobiology Center. Dr. Miller has published more than 370 research papers, serves on the editorial boards of multiple journals, and is internationally recognized for his research on pathogenesis and regulation of autoimmune diseases using antigen-specific tolerance and monocyte targeting strategies.
Inflammatory monocyte-derived effector cells are speculated to play a major pathologic role in the pathogenesis of numerous inflammatory neurological diseases. However, no treatment option currently exists that is capable of specifi cally modulating these cells. We show that intravenously infused 500 nm diameter negatively-charged, biodegradable immune-modifying-nanoparticles (IMPs) formulated from the FDA-approved biopolymer, poly(lactic-co-glycolic) acid (PLGA), are specifi cally taken up by infl ammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer traffi cked to sites of infl ammation, rather, IMP infusion caused their sequestration in the spleen (through apoptotic cell clearance mechanisms) and ultimately caspase 3-mediated apoptosis. Administration of IMPs immediately following disease initiation in mouse models of relapsing experimental autoimmune encephalomyelitis (R-EAE), acute spinal cord injury, epilepsy and lethal West Nile virus encephalitis, markedly reduced monocyte accumulation at CNS infl ammatory foci, signifi cantly reduced disease symptoms and promoted tissue repair. Together these data highlight the intricate interplay between scavenger receptors, the spleen and infl ammatory monocyte function; indicate a major pathologic role for blood-borne inflammatory monocytes rather than CNS-resident microglia in a variety of infectious and non-infectious neuroinflammatory diseases; and support the translation of IMPs for therapeutic use in a range of neuroinflammatory diseases caused or potentiated by inflammatory monocytes.
National Tsing Hua University, Taiwan
Title: Biomarker discovery for neuroendocrine cervical cancer
Time : 11:05-11:25
Hong-Lin Chan is Head of the National Tsing-Hua University (Taiwan) for Quantitative Proteomics Group and has more than 10 years of experience in proteomic method development and application. He received his PhD degree from University College, University of London in 2005. After 2 year Post-doctoral training in the Wolfson Institute for Biomedical Sciences, he took the current Professorship from National Tsing-Hua University in Taiwan. He was one of the first users of 2D-DIGE technology which is routinely used for protein expression profiling and the group has also established platforms which perform quantitative phosphoproteomics and redox-proteomics analysis.
Neuroendocrine cervical cancer is an aggressive butrare form of cervical cancer. The majority of neuroendocrine cervical cancer patients present with advanced-stage diseases. However, the limited numbers of neuroendocrine tumor markers are insufficient for clinical purposes. Thus, we used a proteomic approach combining lysine labeling 2-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) to investigate the biomarkers for neuroendocrine cervical cancer. By analyzing the global proteome alteration between the neuroendocrine cervical cancer line, HM-1, and non-neuroendocrine cervical cancer lines, CaSki cells, ME-180 cells and Hela cells, we identified 82 proteins exhibiting marked changes between HM-1 and CaSki cells, and between ME-180 and Hela cells. Several proteins involved in protein folding, cytoskeleton, transcription control, signal transduction, glycolysis and redox regulation exhibited significant changes in abundance. Proteomic and immunoblot analyses indicated respective 49.88-fold and 25-fold increased levels of transgelin in HM-1 cells compared with that in other non-neuroendocrine cervical cancer cell lines, implying that transgelin is a biomarker for neuroendocrine cervical cancer. In summary, we used a comprehensive neuroendocrine / non-neuroendocrine-cervical-cancer-model-based proteomic approach for identifying neuroendocrine cervical cancer markers, which might contribute to the prognosis and diagnosis of neuroendocrine cervical cancer.
University of Sherbrooke, Canada
Title: Behavioural signatures of neuroinfl ammation
Time : 11:25-11:45
Denis Gris is a head of neuroimmunology laboratory at the University of Sherbrooke QC Canada. He graduated from University of Western Ontario from Dr. Weaver’s laboratory where he studied inflammation after spinal cord injury. Dr. Gris moved to pursue his postdoctoral studies with Dr. Ting at university of North Carolina at Chapel Hills NC USA where he began to investigate role of NLRs in neurodegeneration. His main interest is to discover novel anti-inflammatory pathways within the central nervous systemand use this knowledge to design therapies for neurological diseases including multiple sclerosis amyotrophic lateral sclerosis autism and epilepsy.
Multiple sclerosis is an autoimmune demyelinating disease that aff ects more that 2.5 million people worldwide. Biochemical and in vitro data put forward many therapeutic candidates that have to be verifi ed in vivo models of MS. Experimental autoimmune encephalomyelitis (EAE) is a widely utilized model that replicates many aspects of MS. Th e traditionally used assessment of behavioural outcomes is performed by two independent observers in the blind to experimental setup manner. Such way of assessment is person dependent and allow only evaluate a small number of parameters. Also, the scores oft en are different among different laboratories. Here we propose to utilize 40 parameters behavioural assessment during development and progression of EAE. We used 24hr/day recording of animals before and three weeks aft er induction of EAE. The films were analysed using Clever Sys soft ware. We found dramatic diff erences in behavioural outcomes even within the first week of the EAE induction. First, we noted a significant reduction of total distance walked per day. Mice with EAE walked two-fold less after 1-week post-EAE and four-fold less aft er two weeks of EAE. Hanging behaviour signifi cantly declined (up to 30 fold) in mice within two weeks of EAE. On the other hand, grooming behaviour signifi cantly increased in the fi rst week of EAE. Detailed analysis of mouse activity revealed that mice are most active between 20h and 24h and least active during 11hr and 15hr. In conclusion, we demonstrate that multiple parameter automated analysis of behavioural outcomes may help to validate therapeutic targets and give insights into the mechanisms of the neuroinfl ammation during MS.
Seyed Masoud Hojati
Babol University of Medical Sciences, Iran
Title: Initial presentation of multiple sclerosis in Northern Iran; Is there any comparison to other countries
Time : 11:45-12:05
Seyed Masoud Hojati is currently working at Babol University of Medical Sciences, Iran.
Introduction: Multiple sclerosis (MS) is an inflammatory and neurodegenerative demyelinating disease of central nervous system (CNS). The aim of the present study was to determine the frequency of presenting symptoms in patients with MS to assess the factors associated with these symptoms.
Methods: Demographic and clinical features of 263 patients with clinically deﬁnite MS according to the McDonald criteria who had been admitted to a MS Center from 2001 to 2012 in Babol, northen Iran were reviewed. All the patients underwent a standard neurological examinations. Then, all the clinical findings and demographic variables such as marital statue, age onset, education, place of live, disease duration and initiation pattern collected.
Results: A total of 263 consecutive MS patients with the age range of 17 to 61 yr were examined Optic neuritis with the incidence of 46.8% followed by sensory disturbances were the most prevalent initiating symptoms. Significant difference was found between patients with or without optic neuritis and onset age of the disease (p<0.001); however in other variables there was not any significant difference.
Conclusion: Among the different manifestations optic neuritis was the most common initial symptoms in our study and monosymptomatic pattern was the most frequent pattern. Thus, practitioners/neurologists and ophthalmologists should be aware of this critical issue in this region.
Breathing Labs, Europe
Title: Conditioned PLB as a behavioral management strategy to manage Asthma
Time : 12:05-12:25
Matevz Leskovsek, PhD, is a founder and managing director of Breathinglabs.com, a company that produces human computer interfaces for breathing exercises, breathing games, and breathing entertainment. Dr. Leskovsek specializes in biofeedback, cardio-respiratory interaction, and neurology/brain research. He has led Society of Young researchers of Slovenia through fund raising and organization of an annual Mentor of the year award, that has been, among others, praised by the leading scientific journal Nature (Slovenian Scientists Reward Mentors, Nature, 09th June 2011).
Immune response in asthma has a specific signalling pathway that starts with T cells activation and ends in a fully expressed asthmaspecific inflammation. To suppress this immune response big pharma has been designing drugs to target various points in its pathway, mainly T cells, IL cells and TLR cells. Unfortunately such an suppresive intervention also affects patient’s healthy immune response that may result in reduced overall immunity.1 Pursed Lip Breathing (PLB) is a behavioral intervention that is already recommended during asthma attacks and breathing difficulties by most asthma associations and specialist groups 2, 3. Conditioned PLB aims to condition patients to create a behavior that suppresses such immune responses before escalating into an asthma attack. Such behavioral intervention has many benefits against pharmaceutical interventions as it does not distort body’s natural immunological pathways. Additionally it Increases the volume of inhaled and exhaled air (vital capacity), it helps all of the stale air to escape from lungs. It lengthens the time for which the airways remain open and thus less effort is required for breathing. It leads to better alveolar exchange of gases and thus more oxygen can enter the bloodstream and more carbon dioxide can exit.It relaxes the body by increasing the parasympathetic nervous system.
University of Madras, India
Title: Circulating signatures in patients with Parkinson’disease – a concrete search
Time : 12:25-12:45
Dr. A.J. VANISREE, Assistant Professor in Biochemistry, University of Madras had completed Ph.D (2000) in the field of lung cancer. Her Post-doctoral works revolved in the area of gene synteny and immunosuppressant in the reputed National Institutes. After joining University of Madras in 2004, her research interests are focused in the arena of neuro-oncology and neurodegeneration. She had guided more than 8 students for their Ph.D and 30 M.phil degree candidates. She has more than 29 National and international publications in peer reviewed journals . She also had refereed research articles in reputed journals pertained to neuroscience research. Her research findings are presented by her as invited talks in many national and International conferences. She and her lab students have received best paper awards in science meetings. She has funded grants from ICMR, DST and consultancy projects.
Parkinson’s disease (PD), the second most common neurodegenerative disorder affecting, more severely, the aged population is a complicating disease in terms of diagnosis and management. Many investigations have identified biomarkers for accelerating improved diagnosis and tracking of the disease. However, many of them require sound technical expertise and expensive modes of assessment in addition to the problem of the inadequate/lack of accessibility of the brain tissue of PD patients. In view of such scenario we did investigate biochemical and molecular analyses of blood samples from PD patients and found potential candidates which could be validated as peripheral markers for implication in risk assessment, diagnosis and also in assessing the course of the treatment. Understanding the robust link of oxidative stress and neural cell damage in the neurodegenerative process, we assessed the mRNA expression of reportedly highly vulnerable water channel, aquaporin (AQP4) and Phosphatidyl ethnolamine binding protein (PBP), brain derived neurotrophic factor (BDNF) and tropomyosin receptor factor (NTRK2) in the blood samples of PD and non-PD. The study included 140 PD patients and 70 healthy controls. RNA isolation was carried out using blood samples of the subjects recruited in the study and used for qRT-PCR analysis of AQP4, Tyroine hydroxylase as well as PBP. The data were significantly evaluated with SPSS/10 software. Hypothesis testing method was performed and p values of less than 0.05 were considered to indicate statistical significance. The mRNA expressions of AQP4 and TH were found to be reduced whereas that of PBP was found to be elevated when compared with those of healthy control samples. Further, NMR and MS analyses of the lipid content of the samples had surprisingly revealed a new candidate molecules exclusively present in the PD population. The selected PD candidate genes in the study are anticipated to provide valuable resources for developing and understanding of the molecular mechanism associated with PD and for discovering potential diagnostic/therapeutic/pathological markers for PD, as it is a widely accepted fact that peripheral changes could be considered as marker of brain changes in PD patients.