Scientific Program

Day 1 :

  • Neuroinflammation
Speaker
Biography:

Vicente Felipo is Director of the Laboratory of Neurobiology and of the Program on Neuroinflammation and Neurological Impairment of the Centro de Investigacion Principe Felipe in Valencia (Spain). He has 30 years of experience in research on the mechanisms, diagnosis and treatment of neurological alterations in hyperammonemia, hepatic encephalopathy and by exposure to food and environmental contaminants. He has published more than 300 manuscripts, 3 patents, edited 7 books, organized more than 20 International Symposia and directed more than 26 doctoral theses. He has been first Secretary of International Society for Hepatic Encephalopathy and member of different national and International Committees.

 

Abstract:

Several million patients with liver cirrhosis suffer minimal hepatic encephalopathy (MHE), with psychomotor slowing and mild cognitive and coordination impairments that increase accidents, falls and hospitalizations and reduce their quality of life and life span. MHE is an important clinical, social and economic problem (1).

Hyperammonemia and peripheral inflammation act synergistically to induce these neurological alterations. We have identified some alterations of the immune system associated with appearance of the neurological alterations in cirrhotic patients: increased activation of all subtypes of CD4+ T-lymphocytes and of its differentiation to Th follicular and Th22 (2).

Patients died in HE show neuroinflammation in cerebellum, with activation of microglia and astrocytes and loss of Purkinje cells (3).

We study in animal models the mechanisms by which inflammation leads to neuroinflammation; how neuroinflammation alters neurotransmission and how this leads to cognitive and motor alterations. We identify therapeutic targets and assess whether treatments acting on these targets improve cognitive and motor function in rats with MHE.

Rats with MHE show neuroinflammation in hippocampus, with microglia and astrocytes activation and increased IL-1b and TNFa. This is associated with altered membrane expression of NMDA and AMPA receptors which, in turn, impairs spatial learning and memory. Rats with MHE also show neuroinflammation in cerebellum, associated with altered GABA transporters and extracellular GABA which impair motor coordination and learning in a Y maze.

These alterations may be reversed by treatments that a) reduce peripheral inflammation: anti-TNFa (4,5), reduce neuroinflammation: sulforaphane (6,7); increase extracellular cGMP (8,9).

The mechanisms by which inflammation induces neuroinflammation, how this impairs neurotransmission and leads to cognitive and motor alteration would have common components in different pathologies including chronic diseases associated with inflammation, ageing and some mental and neurodegenerative diseases. Treatments useful to improve these mechanisms in MHE may be also useful in these pathologies.

 

 

Dr. Oksana Tuchina

Immanuel Kant Baltic Federal University, Russian Federation

Title: Microglia activation in animal model of post-traumatic stress disorder
Speaker
Biography:

Abstract:

The central nervous system has historically been considered immune-privileged; however this privileged position mostly consists of adaptive immune responses with restricted access of  infiltrating lymphocytes into the brain parenchyma, while cells of the innate immune system — microglia — are abundant in the brain. Microglia is also considered a key player in many neuroinflammatory conditions. Microglial cells respond to infectious agents such as LPS with reactive phenotype and changes in expression of certain markers such as Iba1. Reactive microglia are also found in the brain during neuroinflammatory processes in  depression, bipolar disorder, post-traumatic stress disorder (PTSD). We used animal model of PTSD in order to test how chronic stress affects the neurogenesis, reactivity of microglial cells as well as their density in the dentate gyrus of the hippocampus and whether hippocampal volume is changing during PTSD. According to our results, 10 days after stress onset the number of Iba1+ microglial cells in the dentate gyrus of the hippocampus increased substantially compared to the control group (Mann–Whitney, p=0,028). However we did not see any inflammatory foci, i.e. microglial nodules. The intensity of Iba1+ staining of as well as the size and shape of cells did not differ from the control group. The hippocampal volume did not change significantly. We propose that neurotoxic or neuroprotective role of microglia cells can change depending on the microenvironment, such as in presence of certain cytokines, interleukins, hormones that lead to corresponding changes in the molecular profiles of glial cells. The particular mechanisms of microglia activation and its role in neurogenesis is discussed.

 

 

 

  • Neuroimmunological Disorders

Session Introduction

Jameelah Saeedi

King Abdullah Bin Abdulaziz university hospital, Saudi Arabia

Title: Neuromyelitis optica spectrum disorders
Biography:

Dr. Jameelah Saeedi is a certified Saudi Neurologist who specializes in Multiple Sclerosis and Neuroimmunological Diseases. She received her medical qualification from King Abdulaziz University in Saudi Arabia in 2001 followed by two-boards in Neurology from Saudi Commission for Health Specialties and the Jordanian Medical Council in 2007. Dr. Saeedi is alumni of University of British Columbia where she pursued her fellowship and training in Neuroimmunology and Multiple Sclerosis with Prof. Peter Rieckman in 2009. In 2010 she received two more fellowships in Electromyography and Boutlinum Toxin Injection treatment from the University of Toronto .She is one of few leading pioneers who holds vast knowledge, experience, sub-specializes and practices Multiple Sclerosis and Neuroimmunological Diseases in Saudi Arabia. She has been working at King Fahad Medical City as a Subspecialty Consultant and KFMC Comprehensive Neuroimmunology Program Director .She is currently working at King Abdullah Bin Abdulaziz university hospital in Saudi Arabia

 

Abstract:

Neuromyeltis optica (NMO) is an immune-mediated inflammatory disease of the central nervous system (CNS)

It typically affects the optic nerves and spinal cord, causing recurrent, severe optic neuritis and/or transverse myelitis. NMO was initially described as a variant of multiple sclerosis (MS). However, it is currently considered a separate disease entity that shares some clinical and radiological features with MS. Some reports have suggested that NMO was misdiagnosed as MS in 30%–40% of cases, especially before aquaporin (AQP)-4 testing was available.

In 2004, NMO-IgG was first reported to be associated with the disease, and its antigenic target is the most abundant CNS water channel termed AQP-4. Since this discovery, the disease spectrum has significantly widened, and some patients are being diagnosed with the disease even without manifesting the typical involvement of the optic nerve and spinal cord.

Multiple diagnostic criteria have evolved over the years, and in 2015, new diagnostic criteria were published, wherein a unified term, NMO spectrum disorder with either positive or negative AQP-4 antibodies, has been used.

Although approximately 80% of NMO patients are positive for serum AQP-4 antibodies, some can exhibit negative results despite using the most sensitive available technique. In this negative group of patients, a new antibody targeting myelin oligodendrocyte glycoprotein (MOG)—a protein expressed in myelin and on the surface of oligodendrocytes in the CNS—has been described.

 During my presentation, I will go over the new diagnostic criteria for NMO, the radiological features of the disease, the differences between anti-MOG NMO and anti–AQP-4 NMO, as well as some practical points in the diagnosis and management of the disease. I will also present real cases that I have encountered during my practice.

 

 

  • Immune system
Speaker
Biography:

Ahmed Ali Hussein completed a master's degree at the age of 26 years in microbiology and immunology from the University of Qadisiyah - College of Science had gotten a master's degree in 2016. It has been published of a number of research's in local and international journals, I have a book about immunology title " Medical Immunology ".  I was assigned to supervise a number of undergraduate graduate studies for the purpose of obtaining a diploma degree, and I also provided a lot of advice to postgraduate students (Masters and PhD) in the field of immunology.

 

Abstract:

There are several sites in the body that do not develop immune responses to pathogens, tumor cells, or histoincompatible tissue transplants, these sites, include the brain, eye, testis, ovary, and placenta, so-called because of mechanisms of immune tolerance that operate to protect the tissues from immune-mediated damage. The central nervous system complying the brain and spinal cord is an essential organ for survival, because the inflammation in these sites can lead to loss of organ function. The blood-brain barrier plays an important role in maintaining the separation of CNS from the systemic immune system but the presence of the blood-brain barrier, does not, on its own, provide immune privilege. Activated immune cells secret molecules that are neurotoxic and the encasement of the brain in the skull does not permit excessive infiltration of immune cells. Neurons are highly susceptible to damage by inflammatory responses and have limited ability to regenerate. Since the brain lacks a lymphatic system, and the immunoregulatory mechanisms in the brain circumvent damage to neurons and supporting cells such as oligodendrocytes and astrocytes. Mechanisms known to operate in the protection of neurons from attack by CD8 + cytotoxic T cells involve lack of expression of HLA class Ia A, B and C receptors by neurons. Astrocytes express cell surface FasL which promotes apoptosis in activated T cells by engagement with Fas. (Figure 1). Another mechanisms known to operate in the protection of neurons from attack by natural killer cells is the induced expression of HLA class Ib G receptors that bind to NK inhibitory receptors such as KIR. Astrocytes upregulate surface PD-L1 receptors which promotes apoptosis in activated T cells by engagement of PD-1 receptors. In addition, microglial cells inhibit T cell proliferation by mediating depletion of tryptophan with IDO (indolamine 2,3-dioxygenase).

 

Biography:

Abstract:

Medicine is a field in science that concerns itself to the improvement of an organism’s well-being by having a catena to the field of Healthcare. It is a branch of science which treats diseases and unriddles illnesses which have no available cure like autoimmune diseases, like Lupus. Lupus or Systemic Lupus Erythematosus (SLE) is a disease where the immune system attacks the body’s own cells mistaking it for a foreign aggregate of a person’s body that usually targets the female population. Due to this, many researches of this disease have focused mainly on female Lupus cases, leaving the affected male population with little knowledge about their case and about themselves. As part of the research enterprise, an introspection among the physical, mental, emotional and social aspects of a male lupus patient was done to promulgate information about the accordant aspects of a person’s self and to see any effects of the disease to the manliness of a male Lupus patient. The research was conducted through In-depth interviews and email interviews of one male lupus patient, having open-ended questions as its cornerstone being a case study. Results of the research were accomplished by sense-making, which furthered the knowledge of male lupus patients being physically deduced, mentally polished, emotionally reliant to God and family, socially selective and still relevantly male.

 

 

  • Neurodegeneration

Session Introduction

Anastasia-Ervina Sela

Technological Educational Institute of Athens, Greece

Title: Traumatic Brain Injury as a risk factor for Dementia: Literature review
Speaker
Biography:

Anastasia-Ervina Sela is a student at the 4th year of Nursing at the Technological Educational Institute of Athens.

 

Abstract:

Dementia is one of the most serious complications of Traumatic Brain Injury. This disease can be mainly caused by road accidents and falls, clearly because the effect of the force on the brain is stronger and the changes in brain function are more radical. A retrospective cohort study, which was approved by the University of California, San Francisco and Human Research Committee and was performed from January 1, 2005, through December 31, 2011 (follow-up, 5-7 years), found that among 51799 patients with trauma, 4361 developed dementia compared with 6610 patients with non-TBI trauma. The correlation of Traumatic Brain Injury and Dementia is evident especially in the larger age groups of the population. In addition, several epidemiological studies suggest that Traumatic Brain Injury (TBI) is a risk factor for Dementia, particularly for Alzheimer’s Disease (AD), although a significant association has not always been detected. There is evidence that in mild and severe Traumatic Brain Injuries most patients have emerged after years Dementia in contrast to those patients who just had a minor injury. In conclusion, Traumatic Brain Injury can be associated to a significant degree with the risk of developing Dementia especially to the people with increased risk. Given the high rates of TBI to the general population serious Dementia prevention measures should be taken in such incidents and clearly to carry out more studies and even longer in order to fully understand the mechanisms that affect between traumatic brain injury and dementia.

 

  • Neurogenesis and Gliogenesis
Speaker
Biography:

Dr. Taguchi obtained her B.Sc. from Tokyo University of Agriculture, in Tokyo, Japan and her Ph.D. from Osaka University Graduate School of Medicine, in Osaka, Japan. She worked as a postdoctoral research fellow and a research associate in Dr. Morris White’s lab at Harvard Medical School, Boston, USA. Dr. Taguchi is interested in the interaction between lifestyle-related diseases such as diabetes and neurological disorder such as dementia. Her lab currently studies on the molecular mechanism of diabetes-associated cognitive decline. She is particularly interested in the roles of neural insulin/IGF1R signaling in cognitive functions and the effects of existing medications on brain functions (drug repositioning ). Dr. Taguchi has received several grants from Grant-in-Aid for Scientific Research on Innovative Areas, Grant-in-Aid for Scientific Research, Grant-in-Aid for challenging Exploratory Research, and private foundations in Japan.

 

Abstract:

The aging systemic milieu leads to a decline in hippocampal neurogenesis and cognitive functions, which also occurs in diabetes. Despite growing concern regarding the potential role of diabetic drugs in neural abnormalities, their effects on progressive deterioration of neurogenesis and cognitive functions remain unknown. Metformin, a biguanide antidiabetic medication is the first-line drug for type 2 diabetes and lowers blood glucose levels by decreasing basal hepatic glucose output and increasing glucose uptake by skeletal muscle through activation of the AMP-activated protein kinase (AMPK). Here we show that prolonged treatment with metformin enhances hippocampal neurogenesis while countering the microglial activation in the context of the combination of aging and diabetes in mice. Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes, it improves hippocampal-dependent spatial memory functions accompanied by increased serine /threonine phosphorylation of AMPK , atypical protein kinase C ζ(aPKC ζ ), and Insulin Receptor Substrate 1 (IRS1) , a major mediator of the insulin/IGF1R signaling,  in the hippocampus. Our findings suggest that signaling networks acting through long-term metformin-stimulated phosphorylation of AMPK, aPKC ζ/λ, and IRS1 serine sites contribute to neuroprotective effects on hippocampal neurogenesis and cognitive function independent of a hypoglycemic effect.

Day 2 :

  • Neuroimmunology

Session Introduction

Keyvan Ghadimi

Isfahan University of Medical Sciences, Iran

Title: The Serum Amyloid β Level in Multiple Sclerosis: A Case-Control Study
Speaker
Biography:

Keyvan Ghadimi has completed his medical education at the Isfahan University of Medical Sciences-Iran. He works in different fields of research. His research fields include Neurology, Neuroscience, Neuroimmunology, Neurosurgery, Neuropsychiatric, and Surgery. He has also been active in statistics and is the dominant SPSS software

 

Abstract:

Background: Multiple sclerosis (MS) is one of the most common autoimmune diseases in adults that cause disability in patients. Different studies were conducted on the more rapid diagnosis of the disease such as measuring serum or cerebrospinal fluid (CSF) contents.

Objectives: The current study aimed at measuring amyloid β (Aβ) serum levels in patients with relapsing-remitting MS.

Materials and Methods: In the current case-control study, the serum levels of Aβ were measured in 48 patients with RRMS and 33 healthy controls using the enzyme-linked immunosorbent assay (ELISA) technique in Isfahan, Iran, from 2014 to 2016. Data analysis was conducted with SPSS.

Results: The mean serum level of Aβ in the case (patients with RRMS) and control groups were 192.75±125.65 and 128.11±85.20 pg/mL, respectively; so serum Aβ levels in the RRMS group was significantly higher than healthy controls (p=0.02). Also, there was a significant positive correlation between the serum Aβ levels and the expanded disability status scale (EDSS) (r=+0.85, p<0.0001).

Conclusions: Owing to the increase of serum Aβ level in patients with RRMS and its significant increase in severe MS cases (higher EDSS scores), so serum Aβ level can be considered as a marker for MS and its progression.

Biography:

Abstract:

We present a case report of a 32-year old woman diagnosed with Opticomyelitis of Devic and Systemic lupus erythematosus (SLE). The onset of neurological symptoms was with optic neuritis that affected both eyes within 2 weeks. Five months later the patient complained from paresthesias in the lower extremities and limited dorsal flexion of the right foot. The neurological deficit progressed in the following days to lower paraplegia and upper paraparesis, retention of urine and faeces, impaired somatic sensation and proprioception below the level of upper thoracic segments. The results from laboratory investigations confirmed anaemic syndrome, increased urea and creatinine, hypokalemia, hypoproteinemia with hypoalbuminemia and increased serum gamma globulines (predominantly IgG), severe proteinuria. The results from cerebrospinal fluid (CSF) investigations demonstrated hyperproteinorachia with extremely high protein fractions, low glucose and potassium levels, mild pleocytosis with increased neutrophils. Serum and CSF oligoclonal bands and positive CSF Aquaporin G 32 times higher than the upper referent limit were found. The association with Systemic lupus erythematosus was confirmed by the increased levels of rheumatoid factor, total ANA, and anti-ds-DNA ANA. MRT of the spinal cord and cranio-spinal region visualized the spinal cord as non-homogenously hypointense on T1, hyperintense on T2 and extremely hyperintense on FLAIR sequences through its whole length up to the bulbar-pontine region, without mass effect. The MRT findings and the specific CSF IgG confirmed the diagnosis Opticomyelitis of Devic. The patient was treated with intravenous immunomodulator agents: corticosteroids, immunovenin, cyclophosphamide and there was partial improvement of the neurological symptoms.

We consider the presented case is of special interest with the comorbidity of an aggressive autoimmune systemic disease and an organospecific disease of the central nervous system. Due to the treatment with immunomodulator agents, the progress of SLE was stopped, the neurological symptoms were improved, although severe neurological deficit persists.

 

 

 

  • Neurosurgery

Session Introduction

Jian-jun Sun

Professor, Peking University Third Hospital, China

Title: Classification, Mechanism and Treatments for spinal canal cysts
Speaker
Biography:

Abstract:

A variety of cystic lesions may develop in spinal canal. These cysts can be divided into intramedullary, intradural, extradural, cervical, thoracic, lumbar, and sacral cysts according to anatomical presentation, as well as arachnoid, meningeal, perineural, juxtafacet, discal, neurenteric cysts, and cyst-like lesions according to different etiologies. Mechanisms of initiation and growth vary for different cysts, such as congenital, trauma, bleeding, inflammatory, instability, hydrostatic pressure, osmosis of water, secretion of cyst wall, and one-way-valve effect, etc. Up to now, many treatment methods are available for these different spinal canal cysts. One operation method can be applied in cysts with different types. On the other hand, several operation methods may be utilized in one type of cyst according to the difference of location or style. However, same principle should be obeyed in surgical treatment despite of difference among spinal canal cysts, given open surgery is melely for symptomatic cyst. The surgical approach should be tailored to the individual patient.

 

Biography:

Abstract:

External ventricular drains (EVD) are widely used to monitor and manage intracranial pressure (ICP). However, the conventional EVD setup cannot monitor ICP when EVD is open for draining cerebrospinal fluid (CSF). In contrast, newly available Camino FLEX ventricular catheter has a double-lumen construct to allow tunneling of ICP sensor through one lumen and CSF drain through another so that ICP monitoring and CSF draining can be achieved simultaneously. A pilot trial of FLEX catheter was conducted to evaluate this new system with a primary goal of ensuring the validity of recorded ICP. In addition, FLEX catheter uniquely enables us, without using additional ICP sensors, to study cerebral vascular responses to acute reduction of ICP and increase of cerebral perfusion pressure (CPP) induced by acute CSF drainage.

 

 

  • Neurogenesis and Gliogenesis

Session Introduction

Jia-yi Li

University of South Australia, Adelaide, SA

Title: ProBDNF inhibits proliferation, migration and differentiation of mouse neural stem cells
Biography:

Abstract:

ProBDNF, a precursor of brain-derived neurotrophic factor (BDNF), is an important regulator of neurodegeneration, hippocampal long-term depression, and synaptic plasticity. ProBDNF and its receptors pan-neurotrophin receptor p75 (p75NTR), vps10p domain-containing receptor Sortilin and tropomyosin receptor kinase B (TrkB) are expressed in neuronal and glial cells. The role of proBDNF in regulation of neurogenesis is not fully defined. This study aims to uncover the function of proBDNF in regulating the differentiation, migration and proliferation of mouse neural stem cells (NSCs) in vitro. We have found that proBDNF and its receptors are constitutively expressed in NSCs when assessed by immunocytochemistry and western blotting. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay showed that exogenous proBDNF treatment reduced mouse NSCs viability by 38% at 10 ng/mL. The migration of NSCs was also reduced by exogenous proBDNF treatment in a concentration-dependent manner (by 90% at 10 ng/mL) but increased by anti-proBDNF antibody treatment (by 50%). BrdU (5-Bromo-2´-Deoxyuridine) incorporation was performed for detection of newborn cells. We have found that proBDNF significantly inhibited proliferation of NSCs and reduced the number of differentiated neurons, oligodendrocytes and astrocytes, while anti-proBDNF antibody treatment promoted proliferation and differentiation of NSCs. In conclusion, proBDNF may oppose the functions of mature BDNF by inhibiting the proliferation, differentiation and migration of NSCs during development. Conversely, anti-proBDNF antibody treatment promoted proliferation and differentiation of NSC.