Scientific Program

Conference Series Ltd invites all the participants across the globe to attend Global Summit on Stroke Birmingham, UK.

Day 1 :

Conference Series Stroke-2015 International Conference Keynote Speaker Howard Prentice photo
Biography:

Howard Prentice obtained his Ph.D. from the University of London, UK and after post-doctoral training in the USA he held faculty position at the University of Glasgow, UK\\r\\nfrom 1993-2000. He then joined Florida Atlantic University in Boca Raton where he is currently Associate Professor of Biomedical Sciences in the College of Medicine.\\r\\nFrom 2013-2014 he was visiting Associate Professor at Harvard Medical School, Boston. He has more than 60 peer reviewed publications. He has been serving on study\\r\\nsections for the American Heart Association and the NIH and on editorial boards of several international scientifi c journals.

Abstract:

There is a major need for new stroke therapies, and current treatments involving tissue plasminogen activator (tPA) are dependent\\r\\nupon administration within small time-window aft er stroke onset. We have employed the neuroprotective agents taurine and\\r\\nS-Methyl-N, N-diethylthiocarbamate (DETC-MeSO) either individually, or as part of particular combination therapies, to elicit\\r\\nneuroprotection in a transient focal ischemia rat stroke model. Individually, taurine can protect neurons against ischemia through\\r\\npreventing calcium overload and through inhibiting pro-apoptotic processes. In our studies on endoplasmic reticulum (ER) stress\\r\\npathways, we have demonstrated that taurine elicits neuroprotection by inhibiting two ER stress pathways, namely ATF6 and\\r\\nIRE-1 pathways, without altering the contribution of the PERK pathway. DETC-MeSO, the active metabolite of disulfi ram, is\\r\\na partial antagonist of glutamate receptors and was previously shown to be eff ective in reducing seizures. In our stroke model,\\r\\nDETC-MeSO administered individually, protected through inhibiting ER stress markers including p-PERK, p-eIF2-alpha, XBP-1\\r\\nand CHOP. Using a multi-drug combination consisting of DETC-MeSO and the stem cell mobilizing agent granulocyte colony\\r\\nstimulating factor (G-CSF), in addition to the preconditioning agent sulindac, we found that infarct size was markedly decreased\\r\\nin the stroke model relative to sham controls. With administration of these agents prior to reperfusion, multidrug treatment was\\r\\nfound, at 4 days aft er the ischemic episode, to elicit decreases in GRP78, eIF-2-alpha and IRE-1, both in core and penumbra. Th e\\r\\nmulti-drug combination was highly eff ective at decreasing infarct size, either under conditions of prior administration, or with\\r\\nadministration of the drug combination 24 hours aft er reperfusion. Our novel therapeutic agents were found to decrease infarct\\r\\nsize, to elicit protection through decreasing levels of pro-apoptotic components and furthermore to diff erentially target specifi c\\r\\nER stress pathways.

Keynote Forum

Xin Wang

Harvard Medical School, USA

Keynote: N-acetyl-serotonin and melatonin offer neuroprotection in experimental models of ischemic injury

Time : 11:30-12:10

Conference Series Stroke-2015 International Conference Keynote Speaker Xin Wang photo
Biography:

Xin Wang is Director of Neuroapoptosis Drug Discovery Laboratory, Department of Neurosurgery, Brigham and Women’s Hospital/Harvard Medical School. She received\\r\\nher PhD from Hebrew University of Jerusalem. She did her Postdoctoral training at University of Michigan and Harvard Medical School. She has published about 70 peerreviewed\\r\\narticles and has served as the Guest Editor, Handling Editor, and Editorial Board Member for a number of peer-reviewed journals, as well as the scientist reviewer\\r\\nfor institutes or foundations including NIH, DOD, BSF, and others, and invited reviewer for 30 peer-reviewed journals.

Abstract:

The identifi cation of neuroprotective agents for stroke remains elusive. We therefore test whether melatonin receptor 1A agonists\\r\\nN-acetyl-serotonin (NAS) and melatonin are neuroprotective in experimental models of ischemic injury.\\r\\nWe demonstrate that NAS and melatonin inhibits cell death induced by oxygen-glucose deprivation or H2O2 in primary\\r\\ncerebrocortical neurons and primary hippocampal neurons in vitro, and/or organotypic hippocampal slice cultures ex vivo. We\\r\\nfurther found that NAS and melatonin reduce hypoxia/ischemia injury in the middle cerebral artery occlusion mouse model of\\r\\ncerebral ischemia in vivo. Our data show that NAS and melatonin are neuroprotective by inhibiting the mitochondrial cell death\\r\\npathway including the inhibition of the release of apoptogenic factors cytochrome c, Smac, and apoptosis-inducing factor from\\r\\nmitochondria to cytoplasm, and activation of caspase-3, -9. Furthermore, pro–IL-1 processing, and activation of caspase -1 are\\r\\nevaluated in melatonin-mediated neuroprotection. Moreover, we demonstrate that the neuroprotective eff ects of NAS may result\\r\\nfrom the infl uence of mitochondrial permeability transition pore opening, mitochondrial fragmentation, as well as the suppression\\r\\nof the autophagic cell death pathway under stress conditions by increasing LC3-II and Beclin-1 levels and decreasing p62 level.\\r\\nTaken together, we conclude that melatonin receptor 1A agonists NAS and melatonin have the potential as the novel therapies for\\r\\nischemic injury.

  • Epidemiology of Stroke and Stroke risk factors and their Impact
Location: Hall 1

Session Introduction

Ihor Huk

Medical University of Vienna, Austria

Title: Neutrophil gelatinase-associated lipocalin (NGAL) - Is it relevant for the characterisation of a vulnerable carotid plaque?

Time : 10:00-10:30

Speaker
Biography:

Ihor Huk is the Director of Vascular Laboratory and Clinical Professor of Surgery, Director of Vascular Laboratory Dept. of Surgery, MUV Medical School. He completed his Post-graduate education from University of Chicago, Heidelberg Special Training: American Society in Parenteral and Enteral Nutrition transplant surgery. Since 1984 he performed more than 550 kidney, liver transplantation Vascular Surgery: Clinical, experimental Research (SPACE-Study), (L-arginine study). He is a member of Austrian Society of Surgery Austrian Society of Angiology Austrian Society of Vascular Surgery Ukrainian Academy of High Education Ukrainian Academy of Sciences and Senate -Zaporizhzhia Medical Postgraduate Academy Honoris causa.

Abstract:

Background: Neutrophil Gelatinase-associated Lipocalin (NGAL), known as a 25 kDa protein released by neutrophils, is recognized as a marker of renal injury. Its potential role in cardiovascular pathologies is currently under intensive investigation. Th e aim of our study was to investigate clinical relevance and possible pathophysiological mechanisms of NGAL in carotid artery stenosis. Methods: Atherosclerotic tissue and peripheral venous blood were collected from 150 patients undergoing carotid endarterectomies and correlated with clinical data, laboratory values and ultrasound fi ndings. NGAL mRNA expression in atherosclerotic tissue was analyzed by PCR. Additionally, NGAL expression and response to NGAL were studies in cell types important for atherogenesis, namely macrophages, endothelial cells, and smooth muscle cells in vitro. NGAL levels were measured in peripheral blood of patients and in cell supernatants by specifi c ELISA. Results: NGAL levels were signifi cantly elevated in patients with vulnerable plaques compared to those with calcifi ed plaques presumably by stimulation of various infl ammatory cytokines. NGAL mRNA expression was higher in patients with symptomatic carotid stenosis compared to asymptomatic patients (71% as compared to 31%). Pro-infl ammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were upregulated by NGAL in human monocytederived macrophages (MDM), human coronary artery smooth muscle cells and human umbilical vein endothelial cells (HUVEC). Moreover, treatment of MDM and HUVEC with tumor necrosis factor-a (TNF-a), Il-1b, oncostatin M (OSM), and IL-33 increased NGAL production in vitro. Conclusion: NGAL is signifi cantly elevated in vulnerable plaques especially in patients with symptomatic carotid stenosis.

Speaker
Biography:

Mykola Salkov has worked as a Neurosurgeon in Dniepropetrovsk Regional hospital (Ukraine). He has also worked as Assistant Professor of Neurological Surgery of the Dniepropetrovsk State Medical Academy (Ukraine). He has completed his PhD in Medical Sciences (Neurosurgery) in June 2005.

Abstract:

Introduction: Trauma of the vertebral arteries in the setting of the cervical spinal injury is one of the reasons of the cerebellar stroke. We investigated the compensatory mechanisms of blood circulation in the vertebral arteries which hinder the occurrence of the stroke. Purpose: Investigation of the mechanisms of the compensation of cerebral circulation in the setting of the trauma of vertebral arteries. Methods: We conducted magnetic resonance imaging examination and angiography of the cervical and vertebral arteries in three patients with a dislocation fracture of the cervical region of vertebral column. In two cases we conducted the morphological examination of injured vertebral arteries, cerebellum and brainstem. Results: In one patient with a dislocation fracture of С4-С5 there was a posttraumatic occlusion of both vertebral arteries. Blood circulation in unaff ected regions of vertebral arteries and brain was conducted through collateral vessels. In one patient there was a dislocation fracture of С3-С4. Unilateral vertebral artery occlusion was found. Cerebral circulation occurred through the contralateral artery and by retrograde blood fl ow. In the patient with a dislocation fracture of С6-С7 one vertebral artery was injured with no evidence of total occlusion. Hemodynamic changes were not found. Morphological examination indicated the presence of injury of the vertebral artery wall at the site of a dislocation fracture and arterial thrombosis. Conclusions: Blood circulation in the vertebrobasilar system in the setting of the trauma of vertebral arteries may occur through collateral vessels or by retrograde blood fl ow. Th rombosis and occlusion occurs in the arteries in the setting of the trauma of vertebral arteries in consequence of a dislocation fracture.

Speaker
Biography:

Ying Li is a Professor at Nanjing Medical University School of Public Health. She has completed over 20 granted studies in reproductive and pharmaceutical epidemiology with over 100 papers and several patents. She studied at CDC under WHO scholarships on reproductive health surveillance and post market surveillance for the safety of drugs in 1996 and 2000. She has received dozens awards and professional honors and serves as Associate Editor for three professional journals.

Abstract:

Purpose: To clarify the eff ect of COC, hypertension, dyslipidemia and susceptibility on the risk of female stroke in order to decrease the risk of female stroke in China. Method: Th is was a population-based multicenter case control study. A prospective cohort study was undertaken in 25 towns in two counties in Jiangsu Province, China. Women (44408) on COC user and 75230 women with an intrauterine device (IUD) were followed up for the incidence of stroke. Th e incident cases of stroke (including cerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage) identifi ed by computerized tomography (CT) or nuclear magnetic resonance (NMR). Two diff erent controls including hospitalized patients and neighborhood were matched to the cases according to age ±3 years; residence and similar date of admission for hospitalized patients. Body weight, height, waist circumference (WC), blood pressure, serum lipids and apolipoproteins were measured. Polymerase chain reaction (PCR) was used to amplify polymorphic gene regions for the genotyping of ACE I/D and ACE 2350. Th e primers and enzyme of AGTA-20C were designed by the PIRA PCR method. Genotyping of 3 SNPs (rs700651, rs10958409 and rs1333040) was performed by the polymerase chain reaction assay with TaqMan probes. Results: Th ere is an increased risk of haemorrhagic stroke among Chinese users of long-term low-dose oral contraceptives which appears to persist long aft er discontinuation. Th e risk of hypertension gradually increased with the increasing cumulative time of COC use in women (P=0.0043), dyslipidaemia, accumulative time of COC use ≥15 years and their interaction increased the risk of hypertension. Hypertension was a most important risk factor for stroke incidence. Th e D allele of ACEI/D polymorphism may be a potential risk allele for stroke. COC users carried the ID+DD genotype that may further increase the risk of stroke especially for hemorrhagic stroke. Our results confi rmed the associations of two GWAS SNPs (rs10958409 and rs1333040), moreover, the risk of hemorrhagic stroke increased by 4.81 and 15.06-folds when risk allele carriers of rs10958409 or rs1333040 who took COC. Th e study assessed the associations of three PAI-1 SNPs and also suggested combined eff ects of these PAI-1 gene variants and COC use on stroke risk in the Han Chinese women. Conclusions: Th e research results have promoted the understanding of the important high risk factors of Chinese female stroke and provide evidence to formulate proper prevention measures for coping with the challenges of and an increased incidence of female stroke.

Yasaman Khalili

Iran University of Medical Sciences, Iran

Title: Case fatality of stroke in Iran: A systematic review and meta-analysis

Time : 12:00-12:30

Speaker
Biography:

Abstract:

Context: Cerebrovascular diseases are the second leading cause of death in the world and more than 85% of their deaths occur in low and middle-income countries. Most of the deaths in this group are related to myocardial infarction and stroke. Objectives: Regarding signifi cant increase in stroke incidence in the world and the scarcity of data about the epidemiology of stroke in Iran, we decided to calculate 28-day case fatality rate of stroke in Iran through a systematic review. Data Sources: We searched electronic international (PubMed, SCOPUS, Web of Science) and domestic (Scientifi c information Databases (SID), IranMedex, Iran doc) databases based on pre search strategy. We searched above mentioned databases from January, 1990 to August, 2012 with no other limitations. Study Selection: All national, provincial, district and community studies which were conducted in Iran and reported 28-day case fatality rate of stroke were assessed by two independent reviewers and studies which used WHO defi nition of stroke were included in this systematic review. Data Extraction: 28-day case fatality of stroke was extracted from 13 identifi ed studies based on stroke subtypes. Meta-analysis was conducted for 9 studies which were reported the fi gure for combination of ischemic and hemorrhagic stroke and also was applied for 2 studies on ischemic stroke subtype. Results: Nine studies reported case fatality rate of both pathologic type of stroke (ischemic and hemorrhagic)with a range of 13.6% to32%, three studies documented case fatality of ischemic stroke (from 7.3% to 15.3%) and one study reported case fatality of hemorrhagic stroke as 37.6%. Th e pooled estimate of 28-day case fatality rate for combination of ischemic/ hemorrhagic stroke was 23.6% (95% CI: 17.7-29.5) and was 13.6% (95%CI:11.8-15.4%) for ischemic subtype. All of the studies reported case fatality rate in the combination of both sexes. Conclusions: Studies on the epidemiology of stroke in Iran is scarce. Case fatality of stroke in Iran is comparable with East Europe and East Asia countries while it is higher than most high income countries. We recommend studies on the root causes of this high fatality and systematic interventions based on the evidence-based guidelines.

Speaker
Biography:

Abstract:

Lessons learnt within 34 years in Sub-Saharan Africa highlight the impacts of genetic factors (plague, ethnicity, sickle cell disease) and exposure to environmental factors (seasons, climate change and variability), host attributes (male gender and age), traditional risk factors (hypertension, diabetes, tobacco, heavy alcohol used and dyslipidemia), infections (HIV, Helicobacter pylori and chlamydia pneumoniae), biomarkers of auto-immunity, infl ammation (fi brinogen and BMP), oxidative stress (oxidized LDL), elevated uric-acid, elevated hematocrit and hemostasis (D dimer) on incident stroke types and mortality. Hypolipemia, younger age, and uncontrolled hypertension are associated with hemorrhagic strokes whereas hyperlipemia, older age, poverty, diabetes, HIV, Helicobacter Pylori, El Nino and sickle cell disease are associated with ischemic strokes and high mortality.

  • Treatment for Stroke

Session Introduction

Saema Ansar

Lund University, Sweden

Title: Cerebral Vascular Signal Transduction: A Novel Strategy to Treat Stroke

Time : 12:10-12:40

Speaker
Biography:

Saema Ansar has completed her PhD at Lund University, Sweden in 2007 and has performed two post-doctoral studies one at Department of Neurology at Heidelberg University, Germany and one at Glostrup Research Institute, Copenhagen University, Denmark. She has well-recognized experience in the field of stroke, vascular research, pharmacology, drug delivery and advanced imaging technology such as MRI. She has outstanding research management, team-leader and supervision skills and has supervised more than 15 graduate and undergraduate students. She has published more than 22 papers in reputed journals and 30 abstracts in international conferences.

Abstract:

Stroke accounts for 1.1 million deaths and is the foremost cause of disability in EU. It is an enormous economic, clinical and social burden; so far therapeutic options are limited. It is clear that new strategies are needed given the disappointing lack of success of the enormous research effort focused on potential neuroprotective agents. Unfortunately, all neuroprotective agents have failed to show any beneficial activity in patients with stroke. Stroke is first and foremost a vascular disease, and our unique focus is on stroke-related responses of the vascular wall. This represents a paradigm shift in approach, which is generating promising results. We recently discovered that inhibition of the MEK signaling pathway in the cerebral vasculature improves acute outcome in all types of experimental stroke. These exciting initial findings are propelling our current research program. To successfully develop our novel treatment strategy, we need to more fully understand the consequences of MEK inhibition on stroke outcome. Whether the benefits of early treatment with MEK1/2 inhibitors persist beyond the subacute phase and not negatively interfere with later recovery processes is not known. Therefore, the aim of this study was to determine the post-stroke consequences of MEK inhibition over extended time periods. Acute treatment with a specific MEK1/2 inhibitor U0126 significantly improved long-term functional recovery, reduced infarct size and promotes neurovascular protection and angiogenesis. These results provide new insights of using this treatment and are therefore a promising strategy for stroke.

Speaker
Biography:

Prof. Josman has completed her PhD from New York University and postdoctoral studies from Hebrew University. She is a Professor of Occupational Therapy in the University of Haifa, Israel. She also serves as Director of their Ph.D. program. Prof. Josman is an internationally recognized leader, scholar and educator in the area of cognitive rehabilitation and published more than 80 papers. Her research investigates cognition, metacognition, executive functions and their influence on everyday life. Her work is based on an ecologically-valid assessment of cognitive impairments to performance-based assessments, utilizing innovative methods and tools, inter alia Virtual Reality, for evaluation and intervention.

Abstract:

University of Haifa, Faculty of Social Welfare & Health Sciences, Haifa, Israel Executive functions are defined as higher-order functions necessary for performing complex or non-routine tasks. Post-stroke people are often encumbered by impaired executive functions which hinder their capacity to return to everyday life functioning. During the rehabilitation process, clinicians strive to engage stroke clients in complex functional activities which are neither time-consuming nor expensive, yet are geared specifically to train and augment executive functions. Employing functional virtual environments is becoming an increasingly important training solution. The current study objectives were to (1) describe the respective executive performance profiles for two samples of post-stroke clients, and (2) to investigate their distinctive performance of acute and home-dwelling stroke clients, using a virtual supermarket platform for assessing executive functions. Method: Two groups were included in this study: 35 acute post-stroke participants (29 men and 6 women, mean age ± SD 65.54, ±11.29 years). The home dowelling group included 24 participants (22 men and 2 women, mean age ± SD = 58.9 ± 5.5 years). Instrument: Virtual Action Planning - Supermarket (VAP-S) is a virtual supermarket developed as a clinically-sound and ecologically valid research tool for assessing executive functions. The VAP-S task performance for each participant is gauged using eight outcome measures recorded by computer. Results: Significant differences were found between the average age and year of education of the two groups. A MANCOVA test revealed significant between group performance differences, F(6, 45)= 6.98, p=.001, ES-η2= .29, with the home-dwelling stroke clients performing better than the acute group. No effects for age and years of education were found. Conclusion: Executive functions, such as efficiency and time performance do improve over time. Is this improvement attributable to the rehabilitation process? Or alternately does brain recovery expedite better executive functioning? Investigating the neural correlates of executive functions during performance of everyday activities is proposed as a further key step in research of people following stroke.

Speaker
Biography:

Dr. Howard Prentice obtained his Ph.D. from the University of London, UK and after post-doctoral training in the USA held a faculty position at the University of Glasgow, UK from 1993-2000. He then joined Florida Atlantic University in Boca Raton where he is currently associate professor of Biomedical Sciences in the College of Medicine. From 2013-2014 he was visiting associate professor at Harvard Medical School, Boston. Dr. Prentice has more than 60 peer reviewed publications. He has been serving on study sections for the American Heart Association and the NIH and on editorial boards of several international scientific journals.

Abstract:

Available stroke treatments are largely ineffective and the time window for efficacy for TPA is limited to a few hours. To investigate new treatments for stroke we have compared administration of the amino acid taurine with a novel multi-drug combination in rodent models targeting both mitochondrial pathways and endoplasmic reticulum (ER) stress signaling pathways. Taurine has been shown to prevent calcium overload in neural cells by blocking transport through calcium channels including the L-, P/Q- and N-type calcium channels and the NMDA receptor channel. In a transient focal ischemia stroke model taurine elicits protection by inhibiting both the IRE-1 and ATF-6 ER stress pathways. Our multi-drug treatment involves three components: 1) granulocyte-colony stimulating factor (G-CSF) which elicits neuroprotection via inhibition of ER stress pathways and by inducing stem cell mobilization 2) DETC-MeSO which acts as a partial NMDA antagonist and prevents apoptosis by inhibiting the PERK pathway but not the ATF-6 pathway and 3) sulindac which has been reported to act as a preconditioning agent and in the stroke model elicits induction of pro-survival proteins including Hsp27 and Akt as well as inhibiting the ER stress pathway component ATF-6. While each of the components of the multidrug treatment individually can elicit protection, lower doses used in combination shoe promise for eliciting synergistic pro-survival responses through targeting of key downstream stress responses. The interventions tested augment expression of pro-survival molecules at the same time as inhibiting important pro-death responses including mitochondrial dysfunction, calcium overload and apoptosis elicited through ER stress signaling.

Speaker
Biography:

Benjamin Chitambira completed his BSc Physiotherapy Honours degree from the University of Zimbabwe in 1995. He also completed a Postgraduate Certificate in Healthcare Leadership from the Open University in the UK in 2014. With over 19 years’ experience as a neuro-physiotherapist, he has been carrying out research on optokinetic chart stimulation as a clinical specialist physiotherapist in the Richard Stevens Stroke Unit for over 8 tears. With over 9 papers published in peer reviewed journals, he has been a peer reviewer for reputable journals and now serves as an editorial board member of peer reviewed journals.

Abstract:

Background: This presentation aims to report on the use of optokinetic chart stimulation based OKCSIB protocol for upper limb recovery in dense acute strokes as well as discuss insights for future research. Methods: The optokinetic chart is made of laminated A4 paper. It consists of repeated bundles of the colours of the rainbow. The chart is placed 20 centimetres in front of a patient’s face. It is moved from side to side at approximately one cycle per second for 3 minutes. This is followed by moving the chart up and down for 3 minutes and then forwards and backwards for another 3 minutes. The affected paralysed hand was also used for aiding balance by holding on during sensory interaction for balance for 3 minutes. This was then followed by 5 repetitions each for specific active-assisted anti-gravity extensor exercises of the upper limb. Results: Dense acute strokes treated by the OKCSIB protocol had statistically significant upper limb recovery when compared to those treated by conventional neurophysiotherapy (P < 0.05). The OKCSIB protocol also led to statistically significant prevention of affected hand spasticity (p < 0.05) Conclusion: Optokinetic chart stimulation shows promise as a novel recovery focused upper limb rehabilitation intervention. The key to these results may be in the restoration of anti-gravity extensor tone by cortico-vestibulospinal descending motor output to the affected upper limb. Further research with fully powered randomized controlled trials is required to provide evidence for its inclusion in future guidelines.

Xin Wang

Brigham and Women’s Hospital/Harvard Medical School, USA

Title: Identification of Melatonin Receptor 1A Agonists as Neuroprotective Agents in Experimental Models of Ischemic Injury

Time : 15:20-15:50

Speaker
Biography:

Xin Wang is Director of Neuroapoptosis Drug Discovery Laboratory, Department of Neurosurgery, Brigham and Women’s Hospital/Harvard Medical School. She received her PhD from Hebrew University of Jerusalem. She did her Postdoctoral training at University of Michigan and Harvard Medical School. She has published about 70 peer-reviewed articles and has served as the Guest Editor, Handling Editor, and Editorial Board Member for a number of peer-reviewed journals, as well as the scientist reviewer for institutes or foundations including NIH, DOD, BSF, and others, and invited reviewer for 30 peer-reviewed journals.

Abstract:

The identification of neuroprotective agents for stroke remains elusive. We therefore test whether melatonin receptor 1A agonists melatonin, N-acetyl-serotonin (NAS), and ramelteon are neuroprotective in experimental models of ischemic injury. We demonstrate that melatonin, or NAS, or ramelteon inhibits cell death induced by oxygen-glucose deprivation or H2O2 in primary cerebrocortical neurons and primary hippocampal neurons in vitro, and organotypic hippocampal slice cultures ex vivo. We further found that melatonin and NAS reduce hypoxia/ischemia injury in the middle cerebral artery occlusion mouse model of cerebral ischemia in vivo. Our data show that melatonin and NAS are neuroprotective by inhibiting the mitochondrial cell death pathway including the inhibition of the release of apoptogenic factors cytochrome c, Smac, and apoptosis-inducing factor from mitochondria to cytoplasm, and activation of caspase-3, -9. Furthermore, pro–IL-1 processing, and activation of caspase -1 are evaluated in melatonin-mediated neuroprotection. Moreover, we demonstrate that the neuroprotective effects of NAS may result from the influence of mitochondrial permeability transition pore opening, mitochondrial fragmentation, as well as the suppression of the autophagic cell death pathway under stress conditions by increasing LC3-II and Beclin-1 levels and decreasing p62 level. Taken together, we conclude that melatonin receptor 1A agonists melatonin, NAS, and ramelteon have the potential as the novel therapies for ischemic injury.

Speaker
Biography:

Makarenko O M has got his PhD degree at the Moscow Medical Stomatological Institute and MD degree from the Institute of Higher Nervous Activity in Moscow. He carries out his Post-doctorate researches at the Institute of Higher Nervous Activity and T G Shevchenko National University of Kiev. He is a Professor of the Psychology Department and the author of more than 100 articles in reputed journals and 4 monographs.

Abstract:

Study was conducted on 30 male rats who were subjected to acute hemorrhagic stroke (HS) simulation. In 10 days with these animals we modeled repeated intracerebral post-traumatic hematoma again. Th e quantitative and qualitative glial analysis of the sensomotor cortex areas of the ipsilateral and contralateral (control) brain hemispheres was carried out: Glial Formula (GF) (the quantitative (percentage) content of glial cells in relation to the total of gliocytes and neurons (GF=astrocytes (A)+oligodendrocytes (O)+microgliocytes (M)); Glial Index Quantitative (GIQ) (a ratio of the sum of one type of gliocytes to another: GIQ1=A/M, GIQ2=O/M, GIQ3=A/O. Th e glial analysis under primary acute HS in the ipsilateral hemisphere in comparison with the contralateral one: GF: Th e number of astrocytes was less (by 34.18%), of oligodendrocytes was less (by 27.97%), of microgliocytes was bigger (by 27.11%) and of pyramidal neurons was less (by 52.13%). GIQ: Decrease of the GIQ1 (by 51.8%), decrease of the GIQ2 (by 18.3%), minor changes of the GIQ3 (by 5.08%). Th e glial analysis under repeated acute HS in the ipsilateral hemisphere in comparison with the contralateral one: GF: Th e number of astrocytes was less (by 64.3%), of oligodendrocytes was bigger (by 37.7%), of microgliocytes was bigger (by 45.75%) and pyramidal neurons were less (by 42.4%). GIQ: Decrease of the GIQ1 (by 79.71%), decrease of the GIQ2 (by 47.7%) anddecrease of the GIQ3 (by 82.4%).

Andreas H. Leischker

Alexianer Krefeld GmbH, Germany

Title: Nutrition in acute stroke

Time : 16:40-17:10

Speaker
Biography:

Andreas H. Leischker studied medicine at University Mainz, Germany and Memorial University Newfoundland/Canada. After completing his residency in Internal Medicine in Frankfurt/Germany he specialized in Geriatrics and Internal Medicine. He worked as consultant in Internal Medicine in Germany and at King Faisal Specialist Hospital and Research Centre in Riyadh/Saudi Arabia. He is leader of the working group “Neurology” of the German Geriatric Society, Head of the Department of Geriatrics, Alexianer Krefeld GmbH and Head of the geriatric rehabilitation Department of the Alexianer Tönisvorst GmbH

Abstract:

Nutrition is of upmost importance in patients with acute stroke. Delivery of nutrition as well as withholding nutrition may seriously harm patients with acute stroke. In contrast to many other diseases, there were no clinical guidelines on nutrition in acute stroke.. In clinical practice, nursing staff, speech-language therapists, nutritionists and physicians are often unassertive how to deliver nutritional support for patients with acute stroke. Key questions include the timing of enteral nutrition, screening and assessment for dysphagia, indication and timing of placement of nasogastric tube versus PEG for stroke patients, swallowing training during in patients with nasogastric tubes, oral nutritional supplements, and texture modification/thickening of fluids. The author (AL) was asked by the steering committees of the German Society for Neurology, the German Society for Nutritional Medicine and the German Geriatric Society to develop evidence based guideline on nutrition for patients with acute stroke. This guideline was published 2007. To our knowledge, this was the first clinical guideline on this topic. Implementation of the guideline in Germany changed clinical practice significantly: For example it was clinical practice to place a PEG tube in patients with severe dysphagia early, after implementation the placement of nasogastric tubes was state of the art. The guideline was updated starting 2010 and finally published in English language 2013. Currently, a European ESPEN guideline on this topic is in progress.

Vidyasagar Casikar

University of Sydney, Australia

Title: STROKE: A Neurosurgeon’s Perspective.

Time : 17:10-17:40

Biography:

Abstract:

Neurosurgeon views stroke to identify any underlying surgically correctable pathology. This talk describes my personal opinion regarding the surgical management of stroke. Vascular accidents such as aneurysms, AVMs and angiomas constitute a major proportion of surgical problems. Recent technical developments have changed the approach to these problems. Haemorrhage in a malignant tumour is not uncommon. Often the diagnosis is delayed due to difficulties in recognising this condition. Surgical treatment of intracerebral haemorrhage is still a controversial subject. The outcome of such a treatment is often poor. Role of surgery in acute cerebellar bleed is limited. Decompression to reduce raised ICP has improved the survival rates. The neurological improvement and quality of survival are generally disappointing. Endovascular treatment of vascular occlusion has encouraging results. The attractive concept of revascularisation is not always supported by favourable outcomes. The presentation highlights the changing trends in the surgical management of strokes.

  • Imaging and Diognosis and Acute Stroke Management

Session Introduction

Sikha Saha

University of Leeds, UK

Title: Use of stroke model in pathophysiology and early diagnosis

Time : 11:30-12:00

Speaker
Biography:

Dr Sikha Saha is a Biomedical Scientist with a background in Physiology and Biochemistry. Her research interests include drug delivery, metabolic profiling and toxicity testing using a novel 3D in vitro BBB model and preclinical testing of novel drugs and diagnostic devices using in vivo models of stroke and neurodegenerative diseases. Her work has led to more than 80 publications in peer review journals and international conferences. She is a lead inventor of a biomaker patent and a co-inventor of a patent with the formation of a spin-off company.

Abstract:

Stroke remains the world’s leading cause of death and disability for which no early diagnosis or effective therapies are available. The increasing prevalence of ischemic stroke and related health risks, combined with the lack of early diagnosis and effective therapies, highlight the desperate need for continued preclinical research to understand the pathological mechanisms of this devastating disease which may enable the development of novel therapeutic targets. However, stroke induced early events and pathological mechanisms remain poorly understood. This is primarily due to lack of clinically relevant models that are highly reproducible as the pathophysiology of cerebral ischemia in animal models is modulated by numerous indirect or secondary factors including the species, type of blood vessels occluded, occlusion period and reperfusion time. We have now optimised murine models of stroke and examined neuronal degeneration and neurochemical changes in these models. These models show consistent pathological and neurochemical changes. In collaboration with the engineering team at the Leeds University, we have also developed bio photonic technologies using lasers with skin safe wavelengths for detection of biomarkers in stroke.

Speaker
Biography:

Nany Hassan Abu Al-Makarim is Lecturer of Internal Medicine, Geriatrics Department at Alexandria University, Egypt. She has done her MS in Rheumatology and MD in Geriatrics.

Abstract:

Objective: To evaluate the role of the detection of ischemia modifi ed albumin (IMA) level in the diff erentiation between ischemic and hemorrhagic cerebrovascular stroke. Materials & Methods: Sixty elderly persons classifi ed into three groups, 25 patients diagnosed with cerebral infarction, 15 patients diagnosed with cerebral hemorrhage and 20 elderly healthy persons with matched age as control were enrolled in the study. IMA was measured using the available chemical method and computerized tomography (CT) was done for diagnosis of brain lesions. Results: IMA was signifi cantly higher in patient group than control group. Th ere was positive signifi cant correlation between age, albumin with IMA, (P=0.000 and 0.037 respectively). However there was no statistical signifi cant diff erence between sex and diagnosis cross tabulation (0.51). It was found that, IMA was statistically higher in infarction group than hemorrhage group (P=0.000) and IMD index was statistically higher in infarction group than hemorrhage group (P=0.013). Our investigation in elderly patients suggests that IMA assay is a sensitive marker for early detection ischemic and hemorrhagic stroke.

Speaker
Biography:

Stefan Golaszewski worked as a Neurologist at the University Innsbruck from 1995 to 2001, where he focused on clinical applications for functional Magnetic Resonance Imaging. From 2001 to 2002, he has worked at the Medical University. He has worked as Associate Professor at the Department of Neurology at the Paracelsus Medical University (PMU) Salzburg in Austria since 2005 and focuses on the investigation of cortical reorganization after stroke. Since 2010, he is Medical Head of the Neuroscience Institute of the PMU. He has published 120 papers in international peer-reviewed journals.

Abstract:

Introduction: Th e present study examines the eff ect of whole-hand electrical stimulation on motor recovery in stroke patients at the subacute stage. Peripheral electrical stimulation has been proved to modulate cortical plasticity in healthy and in patients. Such neuromodulatory eff ects have been also found aft er application of electrical hand mesh-glove stimulation (MGS) in our previous studies on healthy subjects. Materials & Methods: Patients with cortico-subcortical ischemic stroke and predominantly motor hemiparesis of the upper extremity were recruited for the study. MGS was applied on the paretic hand daily for 60 min before the standard rehabilitation training over three weeks. Th e hand motor and sensory functions were evaluated with Wolf Motor Function Test, Fugl-Meyer Assessment score, Nine Hole Peg Test and Semmes-Weinstein monofi laments. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to follow the corticospinal excitability changes over the treatment period. Further, functional magnetic resonance imaging (fMRI) was conducted to assess the cortical brain reorganization changes aft er the treatment. Eff ects of MGS were compared to control group receiving sham stimulation. Results: Patients form both groups showed signifi cant functional improvement as assessed with the motor functional tests. However the improvement degree for the MGS group was increased compared to the control group. Th ese functional eff ects correlated with neuroplastic changes within the sensorimotor area as revealed by TMS and fMRI. Discussion: Electrical stimulation applied before a physiotherapeutic training raise the motor cortical excitability in the lessoned cortex so that the subsequent training becomes more eff ective. Th e obtained results provide better understanding how modulation of central motor controlling structures by somatosensory stimulation correlates with the functional motor recovery.

Speaker
Biography:

Abstract:

Background: rTPA showed level-1 benefi t in AIS. Intracarotid-sodium-nitroprusside (ICSNP)studied here for widetreatment- window and fast-recovery. 1. Retrograde-Neurotransmission-RNT (acute); Normal-impulse: At synaptic-level, glutamate-activates NMDA-receptors having nitric-oxide-synthetase (NOS) on post synaptic-neuron, for further propagation by calcium-calmodulin complex. Nitric-oxide (NO-produced-by-NOS) travels-backward across chemical-synapse (CS), binds NO-receptor/sGC of presynaptic-neuron, regulating anterograde-neurotransmission (ANT). Heme (ligand-binding-site) exhibits >10,000-fold higher affi nity for NO than for oxygen (10,000-fold-eff ect). Stroke: Normal synaptic-activity, ANT and RNT are absent. NO-donor (SNP) releases NO from NOS. NO travels backward across CS to bind heme of NO-receptor/sGC, generates Electrical-Impulse as in normal-ANT. Vasospasm (acute): Juxtrapenumbra- perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP-pathway. Long-Term Potentiation (LTP) chronic: Via NO–cGMP-pathway. Aims/Study design: To treat acute-stroke by RNT/vasodilatation and chronic-stroke by LTP. Case control prospective study. Materials & Methods: 200-patients (100-control and 100 patients ICSNP group). Mean time for superfusion was 9.5 days poststroke. Status was monitored by NIHSS, MRI and TCD. Results: Aft er 90-seconds in ICSNP group, mean change in NIHSS score decreased by 1.44-points/6.55%; aft er 2 hour, decreased by 1.16-points; aft er 24 hour, increased by 0.66-points/2.25%, compared to control-group increase of 0.7 points or 3.53%; at 7 days, 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points or 22.37%; at 2 months 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points or 8.78%. Conclusions: ICSNP is a swift -acting drug in the treatment of stroke, acting within 90 seconds on 9.5 post-stroke days with a small decrease aft er 24 hours then to normal in due course.

Alok Sharma

Neuro Gen Brain & Spine Institute, India

Title: Role and clinical results of Stem Cell therapy in the management of stroke

Time : 14:30-15:00

Speaker
Biography:

Alok Sharma is a Neurosurgeon and presently Professor & Head of Department of Neurosurgery at the LTMG Hospital & LTM Medical College, Director of the NeuroGen Brain & Spine Institute and Consultant Neurosurgeon at the Fortis Hospital in Mumbai , India. He has authored 12 books, edited 2 books, contributed chapters to 8 other books and has 83 scientifi c publications in medical journals. He has made 146 scientifi c presentations all over the world & has conducted several national and international trials and has been conferred with numerous honors and awards in his distinguished career. He has organized many international and national conferences and regularly conducts handson training workshops on Microvascular Surgery, Neuroendoscopy and Spinal fi xations. He has been committed to both basic as well as clinical research in attempting to fi nd an answer to the problems of paralysis and neurological defi cits that occur following injury and diseases of the nervous system. Is the pioneer of Stem cell therapy in India and has setup the Stem cell and Genetic research laboratory at the LTMG hospital & LTM Medical College. He has also created the NeuroGen Brain and Spine institute which is India’s fi rst dedicated Stem Cell Therapy and Neurorehabilitation Hospital. He has published pathbreaking results of Stem Cell therapy in Pediatric Neurodevelopmental disorders such as Autism and Cerebral palsy as well as in other conditions such as Muscular dystrophy and Spinal cord injury. He is the founder of the “Indian Journal of Stem Cell Therapy” and on the editorial board of 4 other journals. He is the Founding President of the “Stem Cell Society of India” and the Vice President of the “International Association of Neurorestoratology”. His other special interests include Revascularization surgery for cerebral ischemia, Psychosurgery, Stereotactic surgery, Neuroendoscopy, Spinal surgery and Neurotrauma.

Abstract:

Cellular therapy is being widely explored in the management of stroke and has demonstrated great potential. It has shown to help the repair of the central nervous system by promoting angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, we have analyzed the eff ect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs) on 24 patients diagnosed with chronic stroke. Th ese patients were also advised a personalized multidisciplinary neurorehabilitation program. Th ese patients were followed up for minimum of 6 months to maximum of 4.5 years.Th ey were assessed on functional independence measure (FIM) objectively, along with assessment of standing and walking balance, ambulation, and hand functions. On comparison of the PET CT scans performed before and aft er the therapy, Increased FDG uptake was recorded in 3 patients. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. It was found that, patients of the younger groups showed higher percentage of improvement in all the areas. Also, patients who underwent cell therapy within 2 years aft er the stroke showed better changes as compared to the other group. We also found that ischemic type of stroke had better recovery than the hemorrhagic stroke. Th ere were no major adverse events recorded on follow up. Th is study demonstrates the potential of intrathecal autologous cell therapy in improving the prognosis of functional recovery in chronic stroke.