- Federal Center of Brain Research and Neurotechnologies, Russia
- Title:Optimization of MS Care Organization in Countries of Central and Eastern Europe, Including DMTs Biosimilars and gGenerics
- Time :
Many countries within Central and Eastern Europe are classified as having the highest prevalence of MS. Consistent with the global trend, in the absence of reliable tests or biomarkers, progression at early stage remains undiagnosed. Due to diagnostic uncertainty and lack of a universally accepted disease definition, clinicians rely more on retrospective analysis of the clinical symptoms to confirm the diagnosis. Important problems are the lack of a universally accepted definition for different types of MS, including SPMS, as well as a lack of reliable biomarkers for the condition contribute to diagnostic uncertainty. A poor understanding of the underlying disease mechanisms and difficulty in identifying the early signs of progression make disease management more challenging for clinicians. Frequent follow-up of patients and periodic assessment of progression are recommended for the timely identification of patients transitioning from RRMS to SPMS. Progression is evaluated based on the disability status, as measured mainly by the EDSS, however, assessment of cognitive function is also important for diagnosing and evaluating disease progression, as cognitive impairment heavily influences the lives of MS patients. It is important to perform the cognitive testing from the beginning of the MS course. From a Central and Eastern European perspective, these challenges are further complicated by a longer delay in diagnosis of SPMS and fewer treatment options. Many patients are currently being treated with DMTs not working in progressive course of MS (PPMS and SPMS). The off-label use of DMTs with low effectiveness in patients with delayed diagnosis of SPMS increases the economic burden of MS in these countries. The focus should be on early treatment initiation to delay disease progression. The high cost of DMTS is another important problem in countries of Central and Eastern Europe. This limits the use of several products and decrease the number of patients, who can received DMTs covered by state. One of the possible ways of decreasing cost of MS without losing effectiveness and safety of therapy is the use of biosimilars and generics. In Russian Federation we have a long time positive experience of the use of biosimilars and generics of IFNβ, GA, teriflunomide, DMF and fingolimod, based on the data of clinical comparing studies. The special study studied the attitude of MS patients and MS neurologist to the transfer from original products to biosimilars and generics. The key role of MS specialists if forming the positive attitude and adherence to biosimilars and generics. The future developing of biosimilars and generics without lose of effectiveness and safety of therapy could be one of the important future direction in MS care in Central and Eastern Europe.
Dr. Alexey Boyko gained his MD and PhD from the Russian State Medical University, Moscow and has been Professor of the Department of Neurology and Neurosurgery at this university since 1997. He was the Chief Neurologist of the Department of Health Care of the Government of Moscow in 2001-2015. He works as the Director of the Moscow Multiple Sclerosis Centre and Director of the Institute of Clinical Neurology and Department of Neuroimmunology at the Federal Centre of Brain Research and Neurothechnologies. He was also elected as Honourable Professor of Kazan and Yaroslavl State Medical Universities. He is also a member of the Presidium of the All-Russian Society of Neurologists, Co-ordinator of the Medical Consulting Boards of Moscow and All-Russian MS Societies, President of RUCTRIMS, member of ECTRIMS Council, Member of the Board of the European Charcot Foundation (ECF). In 2017 he was elected as Honored Scientist of Russian Federation. He has published 17 books and more than 900 original publications, he is Co-editor of three medical journals, a member of Editorial Boards of 5 journals, including MSJ and MSRD. The main interest is epidemiology and genetic of MS, neuroimmunology, clinical trials in MS, he is a member of several Advisory Boards of ongoing and finished clinical trials.
- Pasteur Institute, France
- Title:Do Nicotinic Receptors Modulate High-Order Cognitive Processing?
- Time :
Recent studies provided strong evidence that deficits in cholinergic signaling cause disorders of cognition and affect conscious processing. Technical advances that combine molecular approaches, in vivo recordings in awake behaving animals, human brain imaging, and genetics have strengthened our understanding of the roles of nicotinic acetylcholine receptors (nAChRs) in the modulation of cognitive behavior and network dynamics. Here, we review the emergent role of nAChRs in high-order cognitive processes and discuss recent work implicating cholinergic circuits in cognitive control, including conscious processing.
Dr. Jean-Pierre Changeux worked on the bacterial regulatory enzyme, l-threonine deaminase which led to the general discovery that chemical signals that regulate the biological activity of proteins act at “allosteric” sites distinct from the biologically active sites(1961)as a Ph.D. student in Jacques Monod Laboratory, and involved a cooperative conformational transition (Monod-Wyman-Changeux 1965) viewed as a general molecular mechanism of signal transduction. His subsequent career led to the chemical identification of eukaryotic acetylcholine nicotinic receptor, the first identified neurotransmitter/drug membrane receptor and ion channel together with the demonstration of its allosteric properties and of its structural homology with prokaryotic receptors. In addition to the novel concept of allosteric modulators that creates a revolution in the field of drug design, he has brought new perspectives on nicotine addiction, the higher function of the brain and their pathologies.
- Vellore EEG Center, India
- Title:Anterior Thalamic Nucleus Stimulation in Intractable Epilepsy: Optimization of Stimulation Parameters by EEG Based Novel Approach
- Time :
Deep brain stimulation (DBS) of anterior thalamic nucleus (ATN) is establishing as an effective adjunctive therapy for patients with intractable epilepsy (IE) not suitable for epilepsy brain surgery and/or vagal nerve stimulation. The judicious selection of DBS parameters (DBSPs) plays a crucial role in the success of ATN-DBS. Conventionally, DBSPs are selected by trial and error requiring multiple sessions and hospital visits warranting a strong need for optimization of the DBSPs with objective assessment of its effects. The author presents an EEG-guided novel and superior approach to the selection of effective DBSPs targeted to induce EEG-desynchronization, which is known to exert potent antiepileptic influence with possibly possession of an additional anti-kindling effect that can suppress or even arrest the ongoing process of epileptogenesis in the patients with intractable epilepsy in addition to exercising control over the intractable seizures. It is further claimed that the innovative EEG-guided approach can successfully optimize the DBSPs resulting in (a) minimum sessions of DBSP adjustments, thereby reducing the frequency of hospital visits (b) minimum side effects and (c) minimum consumption of the device battery; thus, prolonging its life. Preliminary results of the clinical application of the novel approach in the selection of the DBSPs in a small case series have been very promising and encouraging despite which it is strongly recommended that well designed large sized studies are required for its validation and successful clinical outcome.
Dr. Harinder Jaseja has worked as a faculty member in a Medical school for more than 33 years. His main research interest has been in epilepsy and epileptogenesis; in 2013, he was ranked Second in Epilepsy Research in India.
He has published papers on various aspects of epilepsy, especially association of epilepsy with sleep. He had advocated consideration of diagnosis of epilepsy even after the first epileptic attack (in 2009) long before the ILAE definition of epilepsy in 2014 that permits clinical diagnosis of epilepsy even after one epileptic attack associated with a 60% risk of a recurrent attack. Until this definition, clinicians usually waited for occurrence of a second attack thus delaying the initiation of anti-epileptic medication, causing anxiety and stress in the patients due to uncertainty and unpredictability of a second attack.
His current work has been on Deep brain stimulation (DBS) in intractable epilepsy (IE). He has postulated a new target for DBS, namely Pedunculopontine nucleus (PPN), claiming that its stimulation is superior in therapeutic efficacy and success over the conventional DBS of anterior thalamic nucleus (ATN) in patients with IE.
In 2005, he initiated a debate on the epileptogenic potential of Meditation. He has published new guidelines for treatment of patients with cerebral palsy (CP), based on EEG. He has claimed that CP, contrary to popular belief, can change its course and progression with time and therefore, observation of new guidelines, quality of life of patients with CP may be improved. He has studied the effects of vagal nerve stimulation and has shown and claimed its efficacy in patients with CP, post which, CP has been included in the list of indications of VNS, the links to which are: (http://www.aetna.com/cpb/medical/data/100_199/0191.html,http://www.anthem.com/medicalpolicies/policies/mp_pw_a053286.htm).
He has worked on interpretation of an EEG and shown how its misinterpretation can be prevented; further, he has also ideated how the yield of EEG-findings can be enhanced in patients with epilepsy. He has shown that the hallmarks of epileptiform activity namely ‘spike’ and ‘sharp’ waves (which hitherto were considered having same significance) posses differential clinical significance especially in patients with epilepsy.
Interestingly, he has shown that the Indian traditional application of Shoe-smell in Epilepsy has a sound scientific basis. In a small study, shoe smell was reported to posses beneficial effect (reduction in duration and severity) during an epileptic attack.
- Pontificia Universidad Católica, Chile
- Title:Impact of COVID-19 Pandemic on Stroke Severity and Mortality in the South-East of Santiago, Chile
- Time :
Background and purpose: Chile has been one of the most affected countries by the COVID-19 pandemic, with one of the highest case rates per population. This has affected the epidemiological behavior of various pathologies. We analyze the impact of the pandemic on the number of admissions due to stroke, its severity and mortality in Santiago, Chile.
Methods: a multicenter observational study based on the records of the 3 hospitals of the South East health service in Santiago, Chile. We recorded the number of patients admitted for ischemic stroke between 01 January 2020 and 30 June 2020. We grouped the cases into two periods, pre-pandemic and pandemic, according to the setting of the state of emergency in Chile.
Results: 431 patients were admitted with ischemic stroke during the study period. There was a non-significant decrease in weekly admissions (17 vs 15 patients per week). No differences were observed in the proportion of patients with medical treatment (p = 0.810), IVT (p = 0.638), EVT (p = 0.503) or IVT + EVT (p = 0.501). There was a statistically significant increase in the NIHSS on admission (7.23 vs 8.78, p = 0.009) and mortality (5.2% vs 12.4%, p = 0.012). In a multivariate analysis the NIHSS on admission was associated with the increased mortality (RR 1.11, CI 1.04-1.19, p = 0.003).
Conclusion: We found an increase in the severity of ischemic stroke on admission and in-hospital mortality during the pandemic period. The main factor to increase in-hospital mortality was the NIHSS on admission.
Andrés Silva is a Professor of Neurology at Pontificia Universidad Católica (Santiago, Chile). He studied neurology at the Pontificia Universidad Católica de Chile and is a vascular neurologist trained at the Germans Trias i Pujol Hospital (Barcelona, Spain). He is the head of the stroke unit at Sótero del Río Hospital (Santiago, Chile)
- Catholic University of Brasília, Brazil
- Title:The Physical Education and the Infantile Systemic Hyalinosis: A Case Report
- Time :
The purpose of this case report is to present the case study of a child with Systemic Infantile Hyalinosis in the educational attendance specialized in Physical Education and Art (dance). The collection took place through the Teachers’ Field Diary and the interview with the child’s mother. The pedagogical intervention lasted 15 months and took place at the swimming and dance workshops, with two weekly classes in each workshop lasting 30 min each. The intervention was based on Henri Wallon’s theory of emotions and sought freedom of expression, body experience, and the discovery of a body marked by disease and, in many moments, disrespected in its possibilities. At the end of the intervention, there were no gains in mobility and range of motion in terms of motor, which were compromised due to the instability caused by the progressive disease.There were significant gains regarding self-esteem, which were relevant and significantly contributed to a better quality of life of the child. The rarity of the case makes it difficult to compare the results with the other cases of diseases and disabilities, but the good results obtained allow to open the discussion to other illnesses that are often disregarded by Physical Education due to their severity and complexity in view of the paradigms of the arean, including allowing the replication of the study in other children with disabilities or serious illnesses, based on the use of the founding principles of the proposed pedagogical intervention, provided that individual characteristics and needs are considered.
Graduated, Master and Doctor in Physical Education with specialization in Specialized Educational Service for people with disabilities (Autism, Intellectual Disability and Multiple Disability) and in Psychomotricity. Professor at the State Department of Education of the Federal District and former professor at the Catholic University of Brasília. Author of the books: “Henri Wallon and Multiple Disability – a proposal for pedagogical intervention” and “Proposal for bodily intervention for Autists”.
- University of Sao Paulo, Brazil
- Title:Brain-Linguistic Integration for Artificial Intelligence
- Time :
The perception of human language as an integrated process in the brain combines the stimuli collected from the environment with their organization as in a broader context to prepare appropriate responses. This integration is made possible by the universal structure of language, an architecture based on axiomatic (specialized subsystems that collect stimuli) and logic (brain function that aggregates and organizes stimuli). This structure is compared to the use of artificial neural networks, which does not present satisfactory intuitiveness and consistency. In this work, semantics and statistics are applied to semantically evaluable information to contrast the universal consistency of human language and the ideal consistency of AI. It is suggested that the deep learning techniques that guide the algorithms apply the axiomatic-logical principles of the language to overcome interpretability difficulties, making them overlap in the cognitive architecture of biological and intelligent systems. Semantics and statistics placed side by side to show that the ‘key’ to a good information classifier is in the dynamic aspect of the language (process) with access to weights (context values), as it makes the AI invariant to many input transformations and avoids semantic distortion.
Post-doctoral Researcher at the Department of Computation and Mathematics of Faculty of Philosophy, Sciences and Letters of Ribeirao Preto – University of Sao Paulo, FFCLRP-USP, Brazil; Collaborating researcher at Language Institute of University of Campinas, IEL-UNICAMP, Brazil. Faculty Member at Law Department of University of Ribeirao Preto, UNAERP, Brazil. Direct Doctoral degree in Psychology, FFCLRP-USP, Brazil. Doctoral degree program partly completed at Université Paris III, Sorbonne Nouvelle (2010, CAPES-BEX). Internship at École des Hautes Études en Sciences Sociales, EHESS Paris (2012, FAPESP). Undergraduate degrees in Languages and Law. Member of the research center group to advance artificial Intelligence in Brazil, C4AI, Center for Artificial Intelligence, (USP, IBM, FAPESP). Member of the British Wittgenstein Society. Associate Researcher, National Science Network for Education (Rede CpE, Brazil). Review Editor of Frontiers in Mathematical Physics. Member of Editorial Board and Reviewer of International Scientific Journals.
Research interest: Neuroscience; Neurolinguistics; Brain Impairment; Artificial Intelligence; Neurophysiology; Natural Language. Computational Linguistics.
Recent publications: Monte-Serrat, D; Cattani, C. (2021) The natural language for Artificial Intelligence. Elsevier-Academic Press; Monte-Serrat, D. (2021); Monte-Serrat, D. (2021). Operating language value structures in the intelligent systems. Advanced Mathematical Models & Applications, 6(1), 31-44; Monte- Serrat, D. M., & Cattani, C. (2021). Interpretability in neural networks towards universal consistency. International Journal of Cognitive Computing in Engineering, 2, 30-39.
E-mail firstname.lastname@example.org ORCID iD http://orcid.org/0000-0002-4266-8979 ResearcherID URL
– http://www.researcherid.com/rid/D-5222-2017 Curriculum Vitae http://lattes.cnpq.br/1892922460567339
- GVK Emergency Management Research Institute, India
- Title:The Role of 108 GVK EMRI Ambulance Services in the Management of Behavioral Emergencies in the State of Telangana
- Time :
Mental health is a major public health issue that calls for immediate steps by individuals and societies around the globe. Talking about mental health issues has always been considered a taboo, especially in lower-middle income countries. This paper assesses the role of GVK Emergency Management Research Institute (GVK EMRI) 108 Ambulance Services in the management of behavioral emergencies in the state of Telangana, India. Primary data collection was carried out in Devaryamjal village of Medchal District with people from both rural and urban setting. The use of management services for behavioral emergencies are described, and knowledge attitude and practices in communities regarding the use of these services are identified. The impact of the Covid-19 pandemic on the mental health of individuals is considered as well, and recommendations to strengthen 108 services for managing behavioral emergencies are suggested. As GVK EMRI is a first responder organization, understanding its role in the field of behavioral emergencies can fundamentally impact several lives. Findings indicate that mental health problems exist in communities, but individuals are reluctant to seek help. People from the urban setting were more open to talk about the topic. The awareness of 108 as an emergency response service was immaculate and a positive view was held about the services and the organization.
Ms. Eshita Raju Kalidindi is an undergraduate student at the University of San Francisco pursuing Psychology and Entrepreneurship & Innovation. She has been involved in various research projects. Her most recent research project focused on the Role of 108 Ambulance Services in the Management of Behavioral Emergencies in the state of Telangana. She identified the knowledge attitudes and practices of members in the community with regards to behavioral emergencies and provided recommendations to improve the services of 108 in India. In the past she has also identified the correlation between social media usage and depression in young adults and her paper is currently in the publication process. At present, she is currently working with Dr. Johnathan Cromwell at the University of San Francisco on identifying how creative thinking and creative problem solving are influenced by positive and negative emotions.
- Nara Medical University, Japan
- Title:Hypothalamic Neurons Modulate Behavioral Responses to a Potential Threat.
- Time :
Defensive behaviors are evolutionarily conserved responses to threat stimuli. There are two types of threat stimuli, actual and potential. Actual threats such as predators and intruders elicit fight, flight, and freeze responses. Otherwise, a potential threat such as a novel object evokes risk assessment behavior to correct risk information. Many studies have focused on the neural mechanisms underlying fight-flight-freeze responses, while those of risk assessment are hardly understood. Our recent study revealed that hypothalamic perifornical neurons modulate risk assessment behavior in mice. Perifornical urocortin-3 neurons respond to a novel object stimulus and their neuronal activity is associated with the risk assessment of a novel object. The activation of these neurons enhanced risk assessment and burying behavior. Burying is one of the active forms of defensive behavior and is also known to be a marker for repetitive/stereotypic behavior. The ablation of these neurons caused abnormal behaviors, such as gnawing and direct contact with novel objects. These findings indicate that hypothalamic neurons modulate defensive behaviors in response to a potential threat, which is a new function of the hypothalamus.
Dr. Noriko Horii is a Lecturer of Anatomy and Cell Biology in Nara Medical University from 2016‒Present.
From 2006‒2010 she was an Assistant professor of Anatomy and Cell Biology in Nara Medical University and the Assistant professor of Parasitology in Nara Medical University. In 2006 she received a Ph.D. in Kyoto Institute of Technology, Graduate School of Science and Technology
Her Research focus is: Behavioral neuroscience, the extracellular matrix in the brain
She also earned Awards of: Encouragement Award of the Japanese Association of Anatomist (2015), Young Investigator Award of the Japan Neuroendocrine Society (2013)
- Newcastle University, UK
- Title:Increased Telomerase Improves Motor Function and Alpha-Synuclein Pathology In A Transgenic Mouse Model Of Parkinson’s Disease Associated with Enhanced Autophagy
- Time :
Protective effects of the telomerase protein TERT have been shown in neurons and brain. We previously demonstrated that TERT protein can
accumulate in mitochondria of Alzheimer’s disease (AD) brains and protect from pathological tau in primary mouse neurons. This prompted us to employ telomerase activators in order to boost telomerase expression in a mouse model of Parkinson’s disease (PD) overexpressing human wild type -synuclein. Our aim was to test whether increased Tert expression levels were able to ameliorate PD symptoms and to activate protein degradation.
We found increased Tert expression in brain for both activators which correlated with a substantial improvement of motor functions such as gait and motor coordination while telomere length in the analysed region was not changed. Interestingly, only one activator (TA-
65) resulted in a decrease of reactive oxygen species from brain mitochondria. Importantly, we demonstrate that total, phosphorylated and aggregated -synuclein were significantly decreased in the hippocampus and neocortex of activator-treated mice corresponding to enhanced markers of autophagy suggesting an improved degradation of toxic alpha- synuclein. We conclude that increased Tert expression caused by telomerase activators is associated with decreased -synuclein protein levels either by activating autophagy or by preventing or delaying degradation mechanisms which are impaired during disease progression. This encouraging preclinical data could be translated into novel therapeutic options for neurodegenerative disorders such as PD.
Dr. Saretzki graduated from Sankt Petersburg (Russia) University 1982 and did her PhD at the Department of Genetics at the Humboldt-University Berlin (Germany) in 1990.
Since 1990 she was involved in ageing research and worked on telomeres, telomerase, oxidative stress, DNA damage and cellular senescence. Since 2001 she worked at Newcastle University (UK) where she became a lecturer in Ageing Research in 2002. In particular, her research interest were functions of telomerase in cancer and stem cells as well as non-canonical functions of the telomerase protein TERT in mitochondria. She extended this work to non-canonical functions of TERT in brain with an interest in neurodegenerative diseases.
- Ben-Gurion University of the Negev, Israel
- Title:Pyruvate Administration Reducing Lesion Volume, Brain Edema and the Extent of BBB Permeability 24 hours Post-MCAO.
- Time :
Introduction: It is well known that abnormalities elevated glutamate levels in the brain are associated with secondary brain injury following acute and chronic brain insults. As such, a tight regulation of brain glutamate concentrations is of utmost importance in preventing the neurodegenerative effects of excess glutamate. Pyruvate, via blood resident enzyme glutamate-pyruvate transaminase convert glutamate into its inactive form 2-ketoglutarate. This method of reducing excess glutamate, known as blood glutamate scavenging (BGC). The objective of the present study was to investigate the efficacy decrease in blood glutamate concentrations in the injured brain results in reduced cerebral edema, infarct zone and BBB breakdown.
Methods: Eighty Sprague-Dawley male rats were randomly assigned into one of three groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment (n=30), MCAO plus placebo treatment (n=30), and sham operated rats (n=20). The pyruvate was administrated intravenous after MCAO. Equal volumes of isotonic saline without pyruvate were given to the placebo group. The neurological status, brain infarct zone, brain edema, BBB breakdown (by MRI technique) and blood glutamate levels were also evaluated.
Results: Our results showed that rats after MCAO demonstrated reduced lesion volume, brain edema and the extent of BBB permeability 24 hours post-MCAO . Treatment with pyruvate also led to reduced glutamate levels 24 hours after MCAO and improved neurologic recovery.
Conclusion: Glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke.
Academic Education: M.D 2001 – 2007 Shevchenko Moldavian State University Faculty of Medicine; PHD 2018 – presented at Ben Gurion University in Negev, Beer Sheva, Title: “The effect of blood glutamate scavenging by pyruvate on long – term behavioral patterns after acute brain injuries in rats”.
Professional Training: 2007–2009 Therapy Residency, Republican Clinical Hospital, Tiraspol, Moldova; 2012-2017 Anesthesia Residency, Soroka University Medical Center, Beer Sheva, Israel.
Employment History: 2017 – present Attending in Department of Anesthesiology, Soroka University Medical Center, Beer Sheva, Israel. Academic Appointments: 2018-2019 Clinical Instructor, Division of Anesthesiology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel. 2019 – present Lecturer. Division of Anesthesiology and Intensive Care, General Intensive Care Unit, Soroka University Medical Center Faculty of Health Science, Ben Gurion University of the Negev Beer Sheva, Israel. Educational Activities: 2015 – 2016 Pharmacist course, 4 years. Ben Gurion University of the Negev, 2017 – present Medical Student course, 6 years. Ben Gurion University of the Negev, 2018 – present Anesthesiologist resident course. Ben Gurion University of the Negev.
- Virgen del Rocío University Hospital, Spain
- Title:Antibody-Mediated Encephalitis
- Time :
Antibody-mediated encephalitis is a novel entity in neurology on which there are important advances in pathophysiology, diagnosis and treatment, and is currently considered a rare but with increasing frequency.
Its diagnosis is fundamentally based on antibodies, which are usually delayed, so its early diagnosis is important to reduce sequelae and mortality and requires close monitoring for at least two or three years in search of an associated neoplasm.
Its diagnosis is based on epidemiological, clinical, neuroimaging, fluid, electroencephalographic, nuclear medicine, and the antibodies described, but since they are delayed, we move to the level of certainty “Probable Antibody-Mediated Encephalitis” to start treatment in acute phase and thus reduce sequelae and mortality. It should be noted that these antibodies are not found in half of the patients, which further justifies the follow-up of these patients and the approach to alternative diagnoses.
The purpose of this Oral Communication is to review the most relevant aspects of this entity, focusing on the importance of early diagnosis and the need to have Reference Laboratories to improve efficiency in the detection of antibodies, as well as the need for Increase research items to better understand the pathophysiology of this entity and improve prescribed treatments.
Dr. Francisco Jose is graduated from Medical School in 1991 (Sevilla).He completed his training as neurology resident in Hospital Virgen de las Nieves in Granada (1993-6).He received his Ph. D in 2007 with certificate “Cum Laudem”, in University of Sevilla “ Epidemiology in Multiple Sclerosis in the island of Lanzarote and its variations in the last years”.He received his Master’s Degree in Neuroimmunology from University of Barcelona in 2009.He received his Master’s Degree in Direction of Social-sanitary Servicies from University of Extremadura in 2011.He received the University Expert Degree in Neuropsicology, in Pablo Olavide University, Sevilla in 2010.
Title “Neurologist for the future”, by Spanish Neurological Society. Currently he is the secretary of Andalusian Neurological Society.He is also a Clinic Tutor in pre/post-grade formation.He is a Regular copy editor of the Neurología magazine.
- Zhejiang Provincial People’s Hospital, China
- Title:Effect of Hemodynamic Characteristic Changes of the Carotid Artery on 6-OHDA-Induced Parkinson’s Disease Model Rats Treated by Gut-Acupuncture
- Time :
Parkinson’s Disease , is the most common motor relateddisorders up to date. Since
the discovery of levodopa half a century ago, which may cause a ‘‘honeymoon period”as well
as side effects. Recent studies have reported that acupuncture is the most commonly used
complementary and alternative therapy (CAM) for a large number of PD patients besides
standard treatment.In recent years, the development of PD research has been focused on the
gastrointestinal tract and the related ENS. Combining findings from gut-brain axis studies
about early warning gastrointestinal (GI) symptoms in PD and the course of the ‘‘stomach
meridian” in Huangdi Neijing, we employed a 6-OHDA rat model, to elucidate the
mechanisms of acupuncture–mediated amelioration of PD symptoms.Our data show that gut- acupuncture correlates with significantly increased abundance of TH, a marker of DA
neurons compared to untreated rats. Furthermore the area of SNH in the injured side of the
acupuncture group was significantly reduced. PSV of LCCA, LICA,RICA showed that were
significantlyimproved i.e. decreased in the acupuncture group, while the diameter of LICA
and RCCA in acupuncturegroup was narrower. We also found that the PSV was significantly
increased and the vascular diameternarrowed in LCCA and LICA during treatment, whereas
after removing the acupuncture needle the PSVdecreased and the vascular diameter widened. In short,Gut-acupuncture can reduce SNH and influence TH abundance in the SN which
correlatedwith changes of hemodynamic characteristics of the lesioned side. We suggest a
regulatory mechanismwhich may affect the vagus nerve through the ENS and cause the
change of cervical hemodynamics. Itfurther induces low oxygen tension microenvironment
conducive to the proliferation of neural stem cells,which leads to the enrichment of TH in PD
model rats of acupuncture group.
Dr. Li Lihong is an Associate Professor, Master’s tutor,vice-directors.She graduated from
Zhejiang University of traditional Chinese medicine in 2009, and then worked in the
Department of acupuncture and moxibustion of Zhejiang Provincial People’s hospital. She graduated from Zhejiang University of traditional Chinese medicine in 2009, and
then worked in the Department of acupuncture and moxibustion of Zhejiang Provincial
People’s hospital. She has been engaged in acupuncture clinical work for 11 years, and has
been committed to the research on the mechanism of acupuncture and moxibustion on
regulating neuroimmunity. Good at acupuncture treatment of Parkinson’s disease, myasthenia
gravis, depression, anxiety, sleep disorders, tension headache, migraine, facial paralysis and
so on. She has published a textbook of acupuncture and moxibustion, serving as a member of the
sleep Management Committee of the Chinese Acupuncture Association, a member of the
meridian Committee of the acupuncture society, and a member of the pain society of
traditional Chinese medicine.
- Southern Tohoku General Hospital, Japan
- Title:Diagnosis and Treatment of Co-Existence of Pituitary Adenoma and Rathke's Cleft Cyst. ~Results of a Prospective Study~
- Time :
The frequency of coexistence of pituitary adenoma and RCC was reported to be 1.9%, and it was considered to be very rare, and it was found that Rathke’s cleft cyst (RCC) was complicated with the pituitary adenoma at a high rate, since MET-PET became diagnosable to the pituitary microadenoma. Between 2011 and 2014, we initiated a prospective study with concomitant pituitary adenomas in mind in cases of RCC and examined the frequency of concomitant pituitary adenomas associated with RCC. Based on the results, from 2015, we examined the frequency of precedent RCC lesions in cases with pituitary macroadenomas as a prospective of preoperative diagnosis.
Part1: From 2011 to 2014, 308 surgical cases with prospective analysis for patients with RCCs were included. Male: 77 cases, female: 231 cases. The average age was 39-year-old, ranging from 11-year-old to 82-year-old. Basal pituitary hormones and the presence of abnormal findings in the sellar region on 3D-CT were screened for those with symptoms of headaches and dizziness and suspected RCCs. When abnormalities were observed in the screened items, 3T-MRI features including 3D-Flair cube images and hormonal challenge tests were added. If hormonal loading test showed abnormal ACTH, GH secretions, MET-PET was added and fused images with 3T-MRI were created. Surgical treatment of both complicated lesions was performed at the time of surgery, and pathological examination was performed.
Part2: The complication rate of RCC, which is assumed to be the antecedent lesion of pituitary adenoma, was examined for prospective in macroadenoma operation case under the result of Part1.We studied pituitary tumors in 42 consecutive surgical cases from 2015 to 2016. Scores of headache and detailed preoperative medical history were taken with the combination of RCC and adenoma in mind. Radiological image has been added to sensitive methods for detecting RCCs, namely, 64-channel 3D-CT reconstruction imaging and, more 3T-MRI, conventional imaging, plus flair cube 3D and SPGR techniques. As an intraoperative finding, in cases of suspected ruptured RCC, we check the presence or absence of indirect finding not obtained by histology (presence of fissures within the pituitary gland, ruptured foramen, and venous lake of the dura mater).
Part1: From radiological examination and operative findings, 308 cases of RCC were diagnosed. Among them, pituitary adenomas were histopathologically confirmed in 106 cases, 111 adenomas. Therefore, the rate of concomitant adenoma and RCC was 34%. 100 out of 106 pituitary adenomas showed the diameter less than 10mm (microadenoma). Of the 106 cases, 28 had adenoma confirmed by pathological examination alone, and 78 had adenoma visualized by MET-PET, which was also confirmed by surgical pathological specimens. Breakdowns of adenomas were GH production in 40 cases, ACTH production in 36 cases, PRL production in 14 cases, and others in 5 cases.
Part2: Among 42 consecutive surgical cases, 34 cases were diagnosed as pituitary adenomas. Among those 34 cases of pituitary adenoma, complication of RCC was confirmed in 9 cases, which were pituitary adenoma and suspective preceded lesion.
The complication frequency of macroadenoma and ruptured RCC was 26%. Types of adenomas included PRL production (1 case), Gonadotrpin production (1 case), and GH production (1 case), PRL & GH production (2 cases), TSH production (1 case),
plurihormonal adenoma (2 cases), and Null cell adenoma (1 case). Thus, all types of hormone-producing adenomas were seen.
1, Ruptured RCC has the risk of forming pituitary adenomas, and when diagnosing
and treating RCC, it is important to carry out the retrieval considering also the pituitary
2, Approximately 26% of pituitary macroadenomas were expected to form based on ruptured RCCs.
3, In the medical examination of the pituitary adenoma, the combination of RCC is always kept in mind, and precise hearing, endocrine examination, diagnostic imaging are also important for understanding the disease state in deciding the treatment plan.
Dr. Hidetoshi Ikeda Graduated from Tohoku University School of Medicine in 1981. He learned and had training both Neurosurgery and General pathology at Tohoku University and obtained MD and PhD. He worked as visiting scientist at Dept of Neuropathology, University Hospital, Zurich, Switzerland (1992) and at Dept of Molecular biology, Harvard Medical School, Boston, USA (1993). He accomplished more than 2500 cases of transsphenoidal surgery for pituitary tumors at Tohoku University, Kohnan Hospital, Ohara medical center Hospital and Southern Tohoku General Hospital during the period of 1990~2016. For this great achievement and success he had won many prizes, such as “Joseph Lister Research Awards-2015 in Neurology”, “Archimedes Research Award-2015 in surgery”, “Academic Excellence Award-2015”, “Takahashi memorial award in 2016”, and Albert Nelson Marquis Lifetime Achievement Award in 2017.
- Capital Medical University, China
- Title:Accessory Nerve Schwannoma: A New Case Report and Systematic Review
- Time :
Background and Objective: Accessory nerve schwannoma is an exceedingly rare disease. It has not yet been well characterized because of the rarity of this disease. We sought to expend the knowledge of accessory nerve schwannoma by reviewing comprehensive literature and adding to it a new case that is originated from spinal root of accessory nerve at the cerebellomedullary cisterna.
Case description: A 62-year-old woman presented with a 1-month history of the right occipital pain. There were no apparent neurologic deficits in physical examination. A brain Magnetic Resonance image found a well-demarcated mass at the right cerebellomedullary cistern, extending to the cervical 1 level and moderately compressing the medullar oblongata. The mass was completely removed via a right suboccipital craniotomy with cervical 1 laminectomy. A brain Magnetic Resonance image was performed 36 months following operation. There was no radiologic and clinical evidence of regrowth in three-year follow-up.
Conclusions: To date, we report herein 63 cases of accessory nerve schwannomas, which include 62 cases reported from the literature review and a new case reported herein. Only 5 of accessory nerve schwannomas were strictly located at cerebellomedullary cisterna. We present a new case of schwannoma located at cerebellomedullary cisterna. We performed a comprehensive review of accessory nerve schwannoma, describing more cases than those previously reported. This review characterizes a rare disease and increases awareness of this disease among neurologists and otolaryngologists.
- Virginia Commonwealth University, USA
- Title:Microglia-Axonal Interactions and Diffuse Glial Signatures in a Translational Model of Mild Brain Trauma
- Time :
Traumatic brain injury (TBI) is a highly prevalent disease with devastating costs associated with long term morbidity. While this morbidity has been linked to diffuse pathologies, our knowledge regarding these TBI-initiated diffuse pathologies is limited. Further, there are currently no successful therapeutics to treat TBI, despite many promising candidates. The unsuccessful clinical translation of many promising therapeutics has triggered a call for the use of higher-order animal models prior to transitioning to large-scale clinical trials. Due to their high level of homology with humans in terms of systemic inflammatory responses, metabolic rates, and cytoarchitecture, we utilize an adult micro pig model to study the effects of mild TBI in a more translational fashion. Additionally, as thalamic damage has been suggested to play a central role in the pathogenesis of mild TBI and its various symptoms, we focus much of our investigations on the thalamic domain. In this talk we will explore the association between diffuse axonal injury and neuroinflammation, specifically investigating activated microglial process convergence onto injured axonal segments following diffuse brain injury as well as the species variation we have observed in this trauma-induced phenomenon. We will also explore histopathological signatures associated with serum biomarkers in a micro pig model of diffuse traumatic brain injury. These studies were initiated as part of the multi-institute Operation Brain Trauma Therapy (OBTT) consortium.
Dr. Audrey Lafrenaye, P is an Assistant Professor in the Department of Anatomy and Neurobiology at Virginia Commonwealth University (VCU), USA. Her background is in cellular and molecular neuroscience, with focuses on quantitative immunohistological approaches, glial pathology (including microglia, astrocytes and oligodendrocytes), and traumatic brain injury (TBI). Her research is currently funded by the National Institutes of Health and focuses on evaluating the progression and molecular mechanisms involved in diffuse neuronal and glial pathologies following TBI. She is also a site-PI for the Operation Brain Trauma Therapy (OBTT) pre-clinical therapeutic and serum biomarker discovery consortium, which is the only pre-clinical multi-institute consortium of its type in the field. She is an active member of the National Neurotrauma Society and Training, Education and Mentoring in Neurotrauma for the promotion of diversity in neurotrauma research.
- University of Bologna, Italy
- Title:Field Cancerization Therapy with Ingenol Mebutate Contributes to Restoring Skin-Metabolism to Normal-State in Patients with Actinic Keratosis: A Metabolomic Analysis
- Time :
Actinic keratosis (AK) is a skin premalignant lesion, which progresses into squamous cell carcinoma (SCC) if left untreated. Ingenol mebutate gel is approved for local treatment of nonhyperkeratotic, non-hypertrophic AK; it also has the potential to act as a field cancerization therapy to prevent the progression of AK to SCC. To understand the mechanisms of ingenol mebutate beyond the mere clinical assessment, we investigated, for the first time, the metabolome of skin tissues from patients with AK, before and after ingenol mebutate treatment, with high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR). The metabolomic profiles were compared with those of tissues from healthy volunteers. We identified a number of metabolites, the homeostasis of which became altered during the process of tumorigenesis from healthy skin to AK, and was restored, at least partially, by ingenol mebutate therapy. These metabolites may help to attain a better understanding of keratinocyte metabolism and to unmask the metabolic pathways related to cell proliferation. These results provide helpful information to identify biomarkers with prognostic and therapeutic significance in AK, and suggest that field cancerization therapy with ingenol mebutate may contribute to restore skin metabolism to a normal state in patients with AK.
Dr. Valeria Righi is a researcher at the University of Bologna since 2012. She is professor of biochemistry. Her research activity is focused on metabolomics sciences through the use of nuclear magnetic resonance (NMR). She was involved in the study of cerebral cancer pathologies and the gastrointestinal system cancer diseases. Recently, she has focused her attention on skin diseases (in particular those defined as non-melanoma skin cancer) to the study of tissues and bio-fluids and also to diseases linked to behavioural disorders due to food. Metabolomics is a science that allows us to evaluate metabolic changes even when histological analyses do not detect cellular alterations. She held part of her doctorate and post-doc at the “Instituto de Investigaciones Biomedicas Alberto Sols” Madrid (Spain) and she was post doc at the Harvard Medical School of Boston (USA) in 2008-2009. She was awarded by L’Oreal and Unesco in 2009.
She is author and co-author of over 45 publications in high-impact international scientific journals and has presented numerous works at national and international conferences.
- University of Cambridge, UK
- Title:Compounding Nimodipine Oral Suspension for Subarachnoid Hemorrhage
- Time :
What happens when there is an entire patient population, not just a specific patient, which cannot take a commercial pharmaceutical product due to significant adverse effects, although the commercial product has a U.S. Food and Drug Administration-approved indication for the medical problem? What should or can be done in this situation? This presentation discusses this dilemma using subarachnoid hemorrhage as an example of a true documented medical need, and discuss the option and circumstances surrounding the compounding of a nimodipine oral suspension, a U.S. Food and Drug Administration-approved indication for the treatment of subarachnoid hemorrhage.
The learning objectives include the following:
Discuss the need for an oral nimodipine liquid.
Provide options for treating patients with subarachnoid hemorrhage.
Provide information on compounding nimodipine oral suspension to avoid adverse effects.
Dr. Mcelhiney is the Team Lead Compounding Pharmacist and a preceptor for Indiana University Health in Indianapolis, Indiana. It is one of the largest health-systems in the United States, consisting of 20 hospitals and dozens of outpatient clinics and surgery centers.She is an author for the International Journal of Pharmaceutical Compounding and contributing author in pharmacy and medical textbooks. Dr. McElhiney is a full fellow in the American College of Apothecaries (ACA), American Society of Health-System Pharmacists (ASHP), and the International Academy of Compounding Pharmacists (IACP). She has served on several national committees and board of directors in professional pharmacy organizations and received several awards. Dr. McElhiney currently serves as the President-Elect for the American College of Apothecaries.Dr. McElhiney earned a B.S. in Pharmacy from Purdue University in 1984. She earned a Pharm.D. (2002) and a Masters (2012) from the University of Florida.
- The first Affiliated Hospital of Nanchang University, China
- Title:Plasma Trimethylamine N-oxide, A Gut Microbe–Generated Phosphatidylcholine Metabolite, is Associated with Autism Spectrum Disorders
- Time :
The compositions of the gut microbiota and its metabolites were altered in autism spectrum disorders (ASD) individuals. The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) in relation to the risk and degree of the severity of ASD.
Dr. Lijuan Quan graduated from the Nanchangl University ,China in 2011, now she is a deputy director of rehabilitation department of the First affiliated Hospital of Nanchang University, Attending and associate chief physician. She serves on the following committees: She is a standing member of the first committee of rehabilitation assessment professional committee of China association for the rehabilitation of disabled persons. She is a member of the third session of child rehabilitation committee of Chinese rehabilitation association, She is a member of the first session of the advisory committee on rehabilitation medicine of the Chinese association of rehabilitation medicine. She is a member of autism spectrum disorders group, child rehabilitation committee, Chinese academy of rehabilitation medicine. She is the Vice President of the second council of jiangxi disabled persons rehabilitation association. She is the Vice chairman of the second committee of autism rehabilitation professional committee of jiangxi disabled persons rehabilitation association. She is the Vice – chairman of child rehabilitation committee of jiangxi rehabilitation medical association. She is a member of the second board of jiangxi rehabilitation medical association.
- University of Virginia Health System, USA
- Title:Success Stories Using Emergency Telestroke Services
- Time :
The ability to rapidly access and evaluate acute stroke patients is crucial to ensure a good clinical outcome. Time sensitive therapies, including intravenous thrombolytics (tissue plasminogen activator) and thrombectomy endovascular techniques in selected patients can improve outcome by ~30-70% versus no treatment. Telestroke, the use of live remote videoconferencing by a neurologist to distance emergency departments has allowed greater access and expertise in decision making to render these treatment options. In addition, it allows for higher accuracy in patient selection for treatment, ensuring the right treatment is provided at the right time in the right patient.
We will discuss the current state of Telestroke (international) programs, highlighting the successes, and elucidating the remaining barriers and future growth needs in the field. Clinical cases will be presented to illustrate the new neuroimaging techniques in the field (“RAPID” software brain mapping), and endovascular technical advances (stent-retrievers). Emerging acute stroke therapies, including new thrombolytics being tested, will be discussed. Patient clinical outcomes will be explored in terms of financial, humanistic and societal savings.
Dr. Nina J. Solenski, M.D., FAHA is an internationally recognized vascular neurologist with over 25 years of cerebrovascular clinical and research experience. She completed her medical training at Jefferson Medical College, Philadelphia, PA, and medical and neurology residency training at Dartmouth University, NH and at the University of Virginia (UVA), VA. She completed her Cerebrovascular Fellowship training at the University of Virginia, and was awarded a NIH K08 stroke research grant. She is ABPN board certified in General Neurology and Vascular Neurology. She has been practicing since 1993, specializing in development of telestroke and teleneurology programs, stroke in the young patient, and supporting first generation college students interested in the medical field. She has been involved in over 60 clinical stroke research trials over the years. Current projects include developing a national stroke system of care in the Dominican Republic, implementing a state-wide “ECHO” Stroke program to educate primary care physicians on primary and secondary care of stroke patients. She recently was selected for the prestigious American Academy of Neurology “Women in Neurology Leadership” and has served both as the Chair of the UVA Faculty Senate and as faculty representative on the University of Virginia’s corporate Board of Visitors.
- The Scripps Research Institute and Protego Biopharma, USA
- Title:Treating Protein Aggregation Diseases in the Central and Peripheral Nervous Systems: Success and Failure in Familial Amyloidotic Polyneuropathy and Alzheimer’s disease
- Time :
It was clear almost from the first descriptions in Portugal that the hereditary autonomic and peripheral neuropathy endemic in Povoa de Vazim was due to amyloid deposits in peripheral and autonomic nerves. It remained only for the precursor to be identified as transthyretin (TTR) and the mutation characterized. We now know that there are 123 different mutations in the coding region of the protein that are associated with autosomal dominant neuropathic and/or cardiomyopathic syndromes and that without aggregation there is no clinical disease. Over the last two decades therapies directed at reducing or eliminating amyloid formation by reducing the availability of the TTR aggregation substrate have been introduced into clinical practice. Hence liver transplantation, small molecule molecular stabilizers of TTR and oligonucleotide therapies have reduced symptoms and prolonged life for the carriers of the mutations, a major advance in neurologic patient care. Nonetheless, cure has not been achieved and a significant proportion of the patients do not respond to the available therapies, representing a still unmet medical need.
The role of amyloid deposits in the pathogenesis of Alzheimer’s disease, from the very beginning, was far more contentious with the uncertain role of amyloid articulated initially by Hardy and Higgins and then by Hardy and Selkoe in the titles of their seminal papers e.g. “Alzheimer’s disease: the amyloid cascade hypothesis”. The generation of mice transgenic for mutant forms of the Aβ precursor or the mutant enzymes involved in processing AβPP in the autosomal forms of the human disease allowed the development of therapeutics based on blocking the generation of the amyloid precursor or the aggregation of the amyloidogenic peptide. Enzyme inhibitors tested in these models, as well as antibodies directed against the peptide, its oligomers or fibrils, moved from blocking the pathologic changes seen in the transgenic mouse brains to large scale clinical trials. In contrast with the findings in TTR-associated FAP, the results have been disappointing. We now await the results of trials using secretase inhibitors and/or antibodies in subjects who are carriers of genes that produce autosomal dominant AD administered well before the onset of disease, as judged by the age of onset characteristic of their kindred. The results of such trials will provide the final test of the Aβ hypothesis.
Dr. Buxbaum’s laboratory at NYU School of Medicine identified TTR mutations responsible for both autosomal dominant polyneuropathic and cardiomyopathic forms of amyloidosis and developed transgenic mouse models of systemic TTR deposition. At The Scripps Research Institute he continued his extensive clinical and genetic characterization of the cardiomyopathic TTR mutation that is highly prevalent in African Americans. He served as consultant to Foldrx during its development of tafamidis (Vyndaqel, Pfizer). More recently his group has studied the interaction between TTR and Aβ, finding that neuronal production of TTR may have a salutary rather than an adverse effect on the development of Aβ deposits in the brains of both Aβ transgenic mice and humans with AD.
- University of Haifa, Israel
- Title:Understanding the Variability of Vulvar Pain Manifestation: The Manifestation of Neuropathic Pain Symptoms in Provoked Vestibulodynia
- Time :
Provoked vestibulodynia (PVD), is the common chronic pain syndrome characterized by severe pain and tenderness on vestibular touch or attempted vaginal entry during sexual intercourse (dyspareunia). The incidence of PVD is estimated as 12%-16%, but the actual incidence is presumably higher than reported. The etiology of PVD is considered multifactorial, however, no single causative factor has yet been identified. Current efforts to subdivide PVD into sub-groups had led to the allocation of patients into primary and secondary forms of PVD, describing the onset of symptoms in regards to timing of first provoking physical contact. The comparison between these two types demonstrates pain-related personality features, mainly higher anxiety, among primary PVD patients as well as greater neural hypertrophy in the vestibular tissue as compared to those with secondary PVD. However, this distinction does not address mechanism-based etiology and consequently fails to establish diagnostic and treatment guidelines. Despite that the possible role of neuropathic alterations has been suggested, the precise mechanisms of such idiopathic pain disorder is still insufficiently clear. Treatments focus mainly on the pain and its effect on sexual functioning, but wide disparity in treatments efficacy is reported among PVD patients.
This presentation will focus on the notion that several distinctive sub-groups of PVD exists, such that the anatomic location of provoked vestibular pain hypersensitivity and it’s associated with specific features represent different etiological mechanisms in PVD. Data abstained from large sample of PVD patients will be presented to address whether in part of the women, vestibular pain location (circumferential or posterior vestibule alone) and the existence of vulvar allodynia/hyperalgesia and/or general pain-hypersensitivity represent neuropathic changes. Pain response to experimental stimulation (Q-tip and pressure stimuli) and self-reported pain measures (tampon insertion and penetrative intercourse) will serve to reveal whether vestibular neuroproliferation result painful intercourse. The possibility that congenital or acquired neuronal sensory alteration will be discussed form embryologically perspective in which the endodermal neuroproliferation associated with local and systemic pain sensitivity. This presentation will also highlight whether psychosocial features, sexual functioning and cognitive factors such as pain catastrophizing involved in the manifestation of vulvar pain experience. Identifying sub-groups of PVD based on the mucosal and neuropathic changes may allow better understanding about pain variability in women who suffer from chronic pelvic pain and promote individualized management.
Dr. Michal Granot is an associate professor at the Faculty of Social Welfare & Health Sciences, Department of Nursing, the University of Haifa, Israel. Her clinical background has shaped her research activity that focuses mainly on psychophysical assessment of pain modulation processing. As part of a multi-disciplinary team at the Laboratory of Clinical neurophysiology at the Technion and Rambam Medical Campus she investigates psychological, neurophysiological and cognitive features that affect pain perception and modulation in acute and chronic pain conditions, with special emphasis on pain disorders among women, such as chronic pelvic pain. She has been a co-Principal investigator in several research projects that focused on pain variability and the mechanisms that are involved in the transition from acute to chronic pain, using lab tests of pain induced by experimental stimulations combined with pain related personality questionnaires.
- Medical University of Varna, Bulgaria
- Title:In Vitro Model of Ischemic Stroke: Ghrelin and Potential Intracellular Factors Preventing the Secondary Brain Damage and Ameliorating Postischemic Recovery
- Time :
Normal brain function is highly dependent on oxygen supply, and one of the first consequences of ischemia is change in the neural network: acute episodes of hypoxia result in decreased synaptic activity, while the longer periods of oxygen deprive cause neuronal dead. Ischemic stroke, which usually results from cerebral arteries occlusion, leads to neuronal dead in the infarction core. Stroke is the second leading cause of dead above age of 60 years. Annually, 15 million people worldwide suffer a stroke, nearly six million die, and another five million get permanently disabled. Unfortunately, effective specific therapy for the ischemic brain damage is lacking. However, many patients improve in different period of time following stroke, inferring an innate capacity for brain repair. The exact mechanisms of this recovery are not clear but they may include synaptogenesis and adult neurogenesis. To test this hypothesis we used dissociated cortical neurons as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin (Ghr) treatment. Briefly, cultures were exposed to hypoxia for 6 h (pO2 lowered from 150 to 20 mm Hg). Three hours after the re-oxygenation, half of the cultures were treated with Ghr for 24 h, while the other, non-supplemented, were used as a control. All cultures were stained immunocytochemically for detection of the synaptic marker synaptophysin. Hypoxia led to drastic decline of the number and the activity of synapses, followed by partial recovery after return to normoxia, but still below the pre-hypoxic level. Ghr treatment significantly increased synapse density and activity, as compared with the controls or with the pre-hypoxic period. In addition, we investigated the effect of Ghr on the expression of some intrinsic cellular factors important for the regulation of neurogenesis – Pax6 and Zbtb20. Hypoxia reduced the percentage of cells expressing Pax6 and Zbtb20, but Ghr administration during re-oxygenation considerably upregulated their expression. Furthermore, significant number of Pax6-positive cells had features consistent with neuroepithelial/progenitor cells phenotype, which we normally do not observe in mature cultures under normoxic conditions. In conclusion, Ghr stimulates neuronal network connectivity and activity after hypoxia exposure, and activates some endogenous factors promoting neurogenesis in mature neuronal networks in vitro. Though the functional impact of postischemic neurogenesis is yet unknown, it might be a prospective therapeutic target for stroke patients.
Dr. Irina I. Stoyanova–van der Laan graduated in General Medicine at the Medical Academy, Sofia, Bulgaria and specialized at human anatomy and histology. In 1983 she was appointed as an Assistant Professor and later on, in 2004, as an Associate Professor at the Department of Anatomy, Trakia University, Bulgaria. She obtained her PhD in 2002 (thesis “Morphological and neurochemical characteristics of certain primary sensory neurons”). In 2008-2015 she worked as a postdoc at the department of Biomedical Signals and Systems, and the department of Clinical Neurophysiology, University of Twente, the Netherlands. In 2011 she was appointed as an Associate Professor in Human Anatomy and Physiology at the University College Roosevelt, the Netherlands. Since 2015 she is an Associate Professor at the department of Anatomy and cell biology, Medical University, Varna, Bulgaria.
Her research interests are: Neurosciences: different aspects of the structural and functional neuromorphology and their clinical implications. For her achievements she was awarded twice (at International Falk Foundation Symposium of Gastroenterology in Bucharest, Romania, 2000, and at 7th International Symposium on Cytokines and Chemokines (satellite of the 13th World Congress of Gastroenterology), Montreal, Canada, 2005). She is also a member of the editorial boards of two international journals – International Journal of Biomedical Sciences (since 2005), Adipobiology (since 2009), and a reviewer for other scientific journals.
- McMaster University, Canada
- Title:Pathogenesis of Neurotrauma in the Model of Spinal Cord Injury with Future Directions of Neuroprotective Therapies
- Time :
Spinal cord injury (SCI), traumatic brain injury (TBI) and stroke constitute the most important human diseases with no effective treatments which is related to the lack of understanding of the pathogenesis of the disease initiated by the traumatic (SCI, TBI) or by vascular (stroke) events. In the rat model of SCI studied systematically, 3 supervening phases are evident; (1) Acute Phase, lasts 2 days and is characterized by hemorrhage, poorly defined areas of cellular necrosis and edema; (2) Inflammatory Phase, begins on the day 3 with infiltration of the areas of hemorrhage and necrosis by large numbers of M1 type macrophages phagocytizing myelin and red blood cells. Depending on the location of the hemorrhagic necrosis in the injured spinal cord, there are 2 types of inflammation; (i) areas deep in the spinal cord are converted within the 1st week into a cavity of injury (COI) encompassing necrotic debris and fluid infiltrated by M1 macrophages; (ii) in superficial areas granulomatous infiltration from the subarachnoid space including macrophages, fibroblasts and blood vessels form arachnoiditis obliterating the spinal cord. Both COI and arachnoiditis are walled off by progressively severe astrogliosis mounted by the surrounding spinal cord. The severity of M1 macrophage infiltration in the COI peaks at 1-4 weeks and then slowly declines but small numbers are still present at 16 weeks post-SCI. (3) Resolution Phase overlaps with Inflammatory Phase by 12 weeks and leads to formation of mature syrinx from the COI. Arachnoiditis becomes a mature scar devoid of glial cells and macrophages. The unusual severity and extraordinarily long course of inflammation initiated by trauma in the spinal cord is related to locally massive damage to myelin sheaths, a potently immunogenic material. Its phagocytosis by M1 macrophages is associated with their activation and presence of elevated factors of inflammation such as TNF-, IL-1, IFN-, Il-6, chemokines, MMP-8, within the 1st week and their decline in levels later. The lack of M1 to M2 macrophage polarization in COI with concurrent decline in numbers of M1 macrophages during the Resolution Phase suggests that classic immune mechanisms do not play role in inhibition of severity of inflammation but rather the spinal cord tissue reaction, specifically astrogliosis does. This is supported by previous observations on the SCI in the Long Evans Shaker (LES) rat where inflammation is entirely eliminated by 7 days post-trauma. The severity of inflammation in COI with active myelin phagocytosis by M1 macrophages beyond 16 weeks indicates continuous destruction of the surrounding spinal cord and calls for anti-inflammatory treatments to provide neuroprotection beyond trauma. Since the spinal cord reaction confines the inflammation to the COI which is directly connected to the subarachnoid space, infusion of anti-inflammatory drugs; dexamethasone, Serp-1 and M-T7, immunomodulatory proteins derived from Myxoma virus, into the subdural space resulted in reduction of the numbers of macrophages by 50-80%. While dexamethasone was effective in lowering the numbers of macrophages, it was unduly toxic but both Serp-1 and M-T7 were well tolerated by recipient rats. However, when infused intraperitoneally, both proteins had little (M-T7) or no detectable (Serp-1) effect on the levels of infiltrating macrophages in the COI indicating that constant subdural infusion is an effective mode of administration and intravenous administration is not. Importantly, 1 week long infusion reducing numbers of macrophages resulted in persistence of large amounts of un-phagocytized, myelin-rich necrotic debris and numerous red blood cells that would lead to re-igniting of the severe inflammation at the premature termination of anti-inflammatory treatment. Therefore, a much longer than 1 week, subdural infusion needs to be administered to eliminate inflammation and its destructive activity following SCI and also TBI and stroke involving white matter injury.
Dr.Jacek M. Kwiecien completed his DVM (Doctor of Veterinary Medicine) in 1983 from University of Agriculture in Lublin, Poland. He gained his MSc in 1991 from University of Guelph, Canada. He received his PhD in Veterinary Pathology in 1995 from University of Guelph, Canada. He completed his Post-Doc in Veterinary Pathology from 1994-1996 in University of Wisconsin-Madison, USA, Fellow National Multiple Sclerosis Society, USA.
His current Status is: HE is an Associate Professor of Department of Pathology and Molecular Medicine in McMaster University, Canada. He is also one of the Veterinary Research Pathologists in McMaster University.
His research Interests: Pathogenesis of neurotrauma
Animal models of spinal cord injury and of traumatic brain injury
Neuroprotective treatments in neurotrauma
Mechanisms involved in neuroregeneration.