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Introduction: Although central nervous system (CNS) has long been known as an immune privileged site, in common with all other tissues, it requires effective immune mechanisms to protect against infections. More recent data support that certain areas of healthy CNS are continuously monitored by resident microglia and blood-borne immune cells such as macrophage and T-cell to sustain CNS immune surveillance. Interruption of CNS surveillance by lymphocyte traffic inhibition results in injury and infection by viruses such as JC virus, herpes simplex virus, etc. CNS Immune system has to be regulated in a unique way in order to prevent inflammation and autoimmune reactions against CNS derived antigens, which there is no tolerance for them. Conclusion: Here, we discuss the anatomical and cellular aspects of immune surveillance in the CNS. Moreover, we review a new model to explain how antigen-specific T-cell responses occur in the CNS.

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Introduction: Multiple sclerosis (MS) is an autoimmune disease of central nervous system that is characterized by the progressive loss of myelin. In addition to immunoregulatory properties, novel MS therapies promote myelin repair activities. Mesenchymal stem cells (MSCs) have been viewed as a potent tool for regenerative and immunosuppressive functions, indicating a potential therapy for MS. MSCs have immunological functions which are exerted by direct cell-to-cell contacts, secretion of stimulatory and inhibitory cytokines, and/or a combination of both mechanisms. Therefore, these cells can inhibit differentiation and proliferation of T-cell and stimulate the Th2 and regulatory T-cells through inhibitory effects on the immune system. Conclusion: In the current review, we discuss the mechanisms underlying the immunomodulatory effect of MSCs in different experimental models of MS.

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Introduction: Fatigue is considered to be one of the main causes of im‌paired quality of life among patients with multiple sclerosis (MS). Creatine enhances ATP synthesis and possesses antioxidant properties. There has been interest in the use of creatine supplement for fatigue and muscle strength in neurological disorders. It has previously been reported that, using 20 gram/day creatine supplement for 5-7 days followed by 5 gram/day for another 7 days did not ameliorate fatigue in patients with MS. In this study, we aimed to determine whether longer application of creatine supplement would be effective in controlling fatigue in these patients. Materials and Methods: In a double-blind controlled trial, 20 patients with MS with fatigue and mild to moderate disability were randomly assigned to creatine (10 gram, two times a day for 14 days) and placebo (10 patients in each group). Fatigue was assessed at baseline and after 14 days using fatigue severity scale (FSS). Results: No significant differences were observed between FSS score before and after the intervention. Furthermore, no significant difference was observed between the experimental groups in the mean difference of FSS. Conclusion: Creatine supplementation had no significant effect on fatigue score even after longer administration.

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Introduction: Multiple Sclerosis (MS) is a chronic disease of the central nervous system and one of the most common neurological disorders among young adults. Clinical manifestations of MS vary from a benign disease to a rapid progressive disabling disorder. Although headache is not common in MS, an increased incidence of headache has been reported in people with MS. According to high prevalence of primary headache in MS patients and the prominence of its diagnosis in improving the quality of life, our aim was to evaluate the frequency of primary headache in patients with MS. Materials and Methods: 100 patients with multiple sclerosis enrolled in this descriptive study. Age, gender, clinical form of disease, duration, Expanded Disability Status Scale, family history of headache and type of headache according to international headache society criteria (IHS) were recorded. Results: In this study, 48% of MS patients had primary headache. Frequency of migraine was 19% and tension type headache was 29%. There was no significant association between primary headache and MS clinical features. Conclusion: This study points to a high comorbidity of headache and MS in Mashhad. Further studies in larger number of patients are needed to confirm our preliminary investigations.

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Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with unknown etiology. Neurotrophins are polypeptides belonging to the neurotrophic factor family. Neurotrophins mediate cell survival and proliferation in the nervous system. In this study, we determined the production of various neurotrophins, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and glial cell-derived neurotrophic factor (GDNF) in Cuprizone model of demyelination. Materials and Methods: In order to induce demyelination, animals were treated by Cuprizone. The mice were divided into three groups. The first group was treated by Cuprizone for 5 weeks. The second group was treated by Cuprizone for 5 weeks and normal diet for 1 week. The third (control) group received normal diet for 6 weeks. After the mice were sacrificed, cerebral corpus callosum was removed and evaluated for expression of neurotrophic factors by real time PCR and histological evaluation. Results: After five weeks, we detected a significant increase of BDNF and GDNF compared to the control group. No changes were observed in CNTF expression. After six weeks, expression of BDNF and GDNF were decreased but they had still higher levels compared to control group. Conclusion: This study suggests that neurotrophins may play a role in pathogenesis of MS.

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Introduction: Multiple Sclerosis (MS) is the most common neurological disease in young adults. In addition to physical problems, MS is associated with significant psychological effects, such as cognitive, mood, and behavioral deficits. Given the high prevalence of this disorder and effects on cognitive and psychological functions, the aim of the present research was to evaluate the effect of cognitive rehabilitation on cognitive function, memory, depression, and anxiety in patients with MS. Materials and Methods: Six patients with diagnostic criteria for MS, both men and women with the age between 20 and 40 years, at least high school diploma education and having participation motivation were selected. Research tools were included DASS scale, Wechsler Memory scale, and Wisconsin Card Sorting test. The Patients were trained for cognitive rehabilitation for three months. Clinical Results were compared before and after the treatment, and finally, the obtained data were analyzed. Results: Cognitive rehabilitation induced significant and considerable improvement in cognitive functions, memory, anxiety, and depression of all patients. Conclusion: This study suggested the possibility of improvement in the cognitive abilities and psychological health of MS patients by cognitive rehabilitation. This finding emphasizes the necessity of new rehabilitation methods for treatment of patients with MS.

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Introduction: According to the importance of psychological factors in psychosomatic disorders and multiple sclerosis (MS) as well as its importance in early maladaptive schemas in psychological disorders, the present study was aimed to evaluate early maladaptive schemas in patients with psychosomatic disorders and MS and compared that with healthy subjects. Materials and Methods: Research method was ex post facto. This study evaluated 100 patients (50 with MS and 50 with psychosomatic disorder) and compared them to 50 healthy people that completed Young Schema Questionnaire (short form). The study was causal-comparative. Results: The results showed that the average score of vulnerability to harm or illness subscale in people with psychosomatic disorder was higher than healthy people and the average score of emotional deprivation, dependence/incompetence, and failure subscale in patients with MS was higher than healthy group. Conclusion: Early maladaptive schemas should be considered as an important element when comparing patients with psychosomatic disorders and MS with healthy people.

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Multiple sclerosis (MS) is a complex neurological disease and its prevalence is about 2 million in the world. Neuroinflammation plays a key role in MS. Vitamins are essential nutrients that have effective role on immune system including activation of lymphocyte and differentiation of T-helper cell. Vitamin D is a micronutrient that is effective on immune function. Deficiently of Vitamin D is a risk factor for progression of MS and studies indicated that 90% of patients with MS have low level of vitamin D. studies showed that there is a relationship between regulatory T cell (Treg) function and Vitamin D status. T lymphocyte and macrophage population have vitamin D receptors especially immature immune cells of the thymus and mature CD8+ lymphocyte. Tregs can be stimulated by Vitamin D supplementation and increased the frequency of Tregs. Also transforming growth factor (TGFβ-1) interleukin 4 (IL-4) can be stimulated by vitamin D that can suppress inflammatory T cell activity. Generally function of vitamin D related to differentiation and activation status of CD4+ T cells. Therefore, attention on other vitamins can be used as an alternative treatment for immune system dysfunction. In this review the effect of vitamin D supplementation and vitamin A on T cell in multiple sclerosis were focused. Previous studies indicate that proportion IL10+ CD4+ were increased and the ratio between IFN- and IL4+ CD4+ T cell decreased by vitamin D. It has been indicated that high dose vitamin D supplementation did not effect on lymphocyte with a regulatory phonotype and the proportion of CD4+ Treg remained unaffected. According to studies, we suggested that other vitamins especially vitamin A can be effective on T cell. T cells that are instigated by Myelin Oligodendrocyte Glycoprotein (MOG) can be reduced by vitamin A.

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Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease which mediated by various molecular and cellular immune components However Recent reports have shown that coagulation factors that traditionally separate from the immune system might also be involved in MS development and progression.studies on experimental autoimmune encephalomyelitis (EAE) and human MS patients reports alterations of some factors of the coagulation cascade such as fibrin, thrombin, prothrombin, factor X and FXII to confirm that coagulation factors have an important role in pathogenesis of autoimmune inflammatory disorders, recent studies report that Genetic deficiency or pharmacologic blockade of FXII significantly protected from EAE and also fibrin depletion, either genetically or using anticoagulants, significantly reduces neurolinflammation, and axonal damage in EAE. Another important study shows that increase thrombin activity is an early event and increases with progression of neuroinflammatory disease, with noted microglial activation and axonal damage. In this review we aim to evaluate elevated coagulation factors of tissue or blood as a new therapeutic strategy for the treatment of MS or other neuroinflammatoy disorders. As we described some coagulation factors such as fibrin and thrombin are significantly increased in MS and blockade of this factors in EAE improve neurolinflammation, and axonal damage so maybe using anticoagulants in Clinical trials develop treatment of MS.

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Multiple Sclerosis (MS) is an autoimmune disease, which is characterized by demyelination and neuroinflammation. Extracellular Matrix (ECM) have important role in the central nervous system (CNS). Alterations are happening to the ECM after the CNS disorder like MS, Alzheimer and other neural injury. Tenasin-C (TnC) is a glycoprotein that is highly expressed in inflammatory conditions of the CNS and expression of this protein is up regulated in tissues and organs that are affected by inflammation. Currently cell therapy is one of the main hopes for MS treatment. Unfortunately there is no powerful study to examine the correlation between the Cell Therapy and expression of TnC as a dependent variable for investigates of the improvement percent. Transplantation of mesenchymal stem cells to the experimental autoimmune encephalomyelitis (EAE) model and investigate quantity of the TnC before and after cell transplantation. Evaluation of TnC in the experimental autoimmune encephalomyelitis (EAE) model after mesenchymal stem cells transplantation may be useful for MS treatment. 

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Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are chronic inflammatory demyelinating disorders of central nervous system (CNS). While the cause is unclear, the fundamental mechanism is thought to be destruction of myelin sheaths of neurons through immune system. One of the approaches being proposed in EAE therapy is neural stem cells (NSCs) transplantation. Several studies have been conducted, investigating immunomodulatory effects of neural stem cells (NSCs) in order to assess their efficacy in the animal model of MS, but still controversies have remained. Our study aim was to systematically review the existing papers in the field of immunomodulatory Effects of Neural Stem Cell on Multiple Sclerosis. The systematic review was conducted according to the preferred reporting items for systematic reviews guidelines. We searched PubMed and Scopus databases based on the relevant medical subject headings (MeSH) of Immunomodulation, neural stem cell, and multiple sclerosis and all articles before January 2017 were included. The included studies had accurate data for immune mechanisms assessment and almost all reported neurologic clinical score assessment. Totally, 30 articles were eligible to be included in our systematic review out of 233 articles found at initial search. Studies showed exert immune modulation when neural stem cells (NSCs) are transplanted in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Regarding the potent immunomodulatory effects of neural stem cells (NSCs) and their beneficial effects in experimental autoimmune encephalomyelitis (EAE), including their capacity for neuroprotection and Immunomodulation it seems that NSCs may be a new therapeutic method in MS therapy.

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Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system associated to myelin loss and neurodegeneration. Clinically patients suffer from diverse symptoms and face the risk to become wheelchair-bound. At the moment MS is incurable, thus there is an unmet need for therapeutic options. 

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Multiple Sclerosis (MS) is a complex disease resulting from the occurrence of intermingled episodes of neuro-inflammation and degeneration. The temporal and spatial patterns in which these events occur are not well understood as well as the molecular substrates underlying it. Myelin loss and gain, as well as axonal damage are considered crucial events influencing the course of the disease but their cause/effect dependency remains unclear. Numerous recent evidence showed impaired cognitive behaviors both in MS patients and animal models, which would support a profound involvement of neurons in mediating such effects, along to the long-known MS hallmarks like locomotor deficits and slow axonal conductance, attributed mainly to myelin loss. In order to investigate the role of neurons and their functionality in the pathophysiology on MS we took advantage of different animal models of neuro-inflammation and general de- and remyelination, namely the experimental autoimmune encephalitis (EAE) and the cuprizone model, respectively. For both animals we could observe the occurrence of different cognitive impairments including loss of short and long term memory and of high functional cortical abilities. In both animals models we could associate these symptoms to an altered neuronal network excitability and therefore, we pursued pharmacological modulation in vitro and in vivo in order to verify this finding by identifying potential molecular players. Therefore, by using different novel or established compounds we tried to identify new drugable targets and new therapeutic time windows for intervention.

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by widespread inflammation, focal demyelination and a variable degree of axonal and neuronal loss. Ionic conductances regulate T cell activation as well as neuronal function and thus have been found to play a crucial role in MS pathogenesis. Since present therapeutical approaches are only partially effective so far, ion channel modulation as a future strategy was brought into focus. Here, we review the status quo concerning recent findings from ion channel research in MS and its animal model, experimental autoimmune encephalomyelitis. 

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Introduction: Recent studies point to the clinical and research efficacy of saliva as a respected diagnostic aid for observing Multiple Sclerosis. The objectives of this Hypothesis are to identify novel biomarkers recognized to Multiple Sclerosis in early stage in saliva and to determine if the levels of these markers correlate with level of these Cerebrospinal fluid and blood assays and urine of diagnostic in multiple sclerosis. Materials and Methods: In total, 200 MS patients (100 women) will recruit (in early and late level). Paired samples of saliva, cerebrospinal fluid (CSF), blood serum and urine will be collected to detect osteopontin, Melatonin, Uric acid (UA), malonic dialdehyde (MDA) and oligoclonal IgG an using multiplex proteomic immunoassays. Results: we hope to changes of osteopontin, Melatonin, Uric acid (UA), malonic dialdehyde (MDA) and oligoclonal IgG in saliva testing. Conclusion: If these parameters change in secretion of salivary gland we can design Microchip to diagnose MS in early stage with saliva testing.

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Introduction: Multiple sclerosis (MS) is a progressive and autoimmune neurodegenerative disease of the central nervous system (CNS). This disease is renowned through symptoms like inflammation, demyelination and the damage of neurological actions. Melittin is one of components of bee venom and has anti-neuroinflammatory effects. Curcumin also, a dietary spice from turmeric, has outstanding anti-inflammation and neuroprotective effects. Materials and Methods: Experimental allergic encephalomyelitis (EAE) is a widely accepted animal model for MS. EAE is created in animals by injecting the tissue of myelin basic protein (MBP), CNS, or myelin oligodendrocyte glycoprotein (MOG) along with the adjuvant. EAE and MS are similar diseases. EAE was induced in 40 rats randomly placed in four groups of 10: Group 1: Named E-S received normal saline (0.2 mL) every day. Group 2: Named E-mel, received 10 mg/Kg melittin every day. Group 3: Named E-cur, received 100 mg/Kg curcumin every day and Group 4: Named E-cur+mel .The treatments started from the first day of post immunization through GPSH-CFA and lasted until the tenth day. The ELISA and the high performance liquid chromatography (HPLC) were used for the assessment of tumor necrosis factor alpha (TNF-α) and nitrate in rats serum. Results: In this study, we indicated that the treatment of EAE with melittin and curcumin decreased the symptoms of clinical disorder, level of serum TNF-α and the serum nitrates in rat EAE. Conclusion: This activity of melittin and curcumin may be caused by the anti-inflammatory effects and the immuno-modulatory and antioxidant effects of these.

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Introduction: Multiple sclerosis is a chronic neuroinflammatory disease that leads to distribute neurodegeneration in the grey and white matter of the brain.  In MS, age-related iron accumulation, chronic oxidative injury and activation of microglia are key factors to create neurodegeneration. Also concentration of CCL₁₁ is increased in   multiple sclerosis. CCL₁₁ can amplify glutamate mediated neurotoxicity and inhibit neurogenesis. Materials and Methods: A model of Heterochronic Parabiosis is created with joining a sick animal to healthy young animal. Results: It is expected by reducing CCl₁₁, healthy young blood could be effective in slowing and improving disease. Conclusion: Other studies suggest that multiple sclerosis treatment should be based on a combination of anti-inflammatory, regenerative, and neuroprotective strategies. By using heterochronic parabiosis has been shown that, young blood can rejuvenate and improve the regenerative capacity of peripheral tissues and central nervous system in aged animals. GDF₁₁ is a systemic ‘pro-youthful' factor in young parabiont, that promote neurogenesis and rejuvenate regeneration capacity of CNS and promote tissue regeneration.  So it seems high concentration of GDF₁₁ and low concentration of ccl₁₁ in healthy young parabiont may be effective on regenerative capacity of central nervous system in MS animals.

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Introduction: Multiple Sclerosis is an autoimmune disease which demyelinates neurons. It is the leading cause of non-traumatic disability in young adults in many countries. According to the atlas of MS, the number of patients with MS has increased from 2.1 million in 2008, to 2.3 million in 2013. Although several studies have been done worldwide to clarify the epidemiological patterns of the disease, researchers have not yet been able to ascertain the accurate geographical distribution, or the precise prevalence and incidence of MS. Previously, Iran has been classified as areas of low MS prevalence but this rate has significantly increased in the recent years. The latest statistics of MS patients in Khoarasan Razavi province belongs to 2013 [Ghandehari et al.] which the prevalence of MS patients was 36 in 100000. According to the increased prevalence of MS in Iran, updating these statistics is needed. The aim of this study is to investigate the epidemiological features of MS in Khorasan Razavi province in 2017. Materials and Methods: The demographic information of MS patients will be derived from Mashhad, Gonabad, Sabzevar, Torbat Heidarieh and Torbat jam’s medical universities. Results: Now we are collecting our data. They will be published as soon as data collection and analysis finish. Conclusion: In 2013, et al. showed that Iran has the highest MS prevalence in the Middle East and Asia. Updating the present data is necessary for the exact incidence of MS.

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Introduction: Multiple sclerosis (MS) has been recognized as a common neurodegenerative disease that occurs after an Auto reactive T cells against myelin antigens.  Demyelination and inflammation are the main features of this disease. The anti-inflammatory and neuroprotective roles of bone marrow-derived mesenchymal stem cells (BM-MSCs) have been considered as a suitable treatment against autoimmune diseases. Previous studies have shown that treatment with BM-MSCs may regulate immune responses and improve the symptoms in experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis. Therefore, the present study was designed to evaluate immunomodulatory effects of BM-MSCs in the treatment of myelin oligodendrocyte glycoprotein (MOG) 35-55-induced EAE in C57BL/6 mice. Materials and Methods: MSCs were obtained from the bone marrow of C57BL mice, cultured with DMEM/F12, and characterized with flow cytometer for the presence of cell-surface markers for BM-MSCs. Following three passages, BM-MSCs were injected intraperitoneally into EAE mice. Immunological responses of the transplantation were evaluated. Results: The results demonstrated that BM-MSCs transplantation in EAE mice significantly reduced inflammation infiltration and demyelination, enhanced the immunomodulatory functions, and inhibited progress of neurological impairments compared to control groups. Conclusion: This study suggests the potential of BM-MSCs to induce immunomodulatory and anti-inflammatory roles in the treatment of neuroinflammatory disorders.

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Introduction: Multiple sclerosis (MS) is a chronic, autoimmune, and inflammatory nervous system disease. It leads to the loss of myelin in the white matter of brain, spinal cord and optic nerves. As a chronic disease with sudden and unpredictable Side effects and complications of the disease will lead to disability and dependency in life. Causes neurologic symptoms and sig. The purpose of the present study is to examine the mediating role of meta-cognitive beliefs on the Cognitive-executive functions of brain، sleep disorders ، optic neuritis in Multiple Sclerosis Patients. Materials and Methods: This is an exploratory-correlative study in which new correlations between variables will be examined. The statistical population includes patie nts suffering from Multiple Sclerosis Patients referred to khorasan razavi Ms Society 100 consecutive referrals (74 women, 26 men) were selected through purposeful sampling. All participant ts completed Perfectionism Cognitions Inventory (PCI), Dysexecutive (DEX) questionnaire. Standard questionnaires quality of sleep and severity of the insomnia ) (ISI) ) The patients underwent clinical tests of visual functions, including visual acuity, contrast sensitivity and color visio Data analysis was done through Pearson's correlation coefficients, two-steps regression analyses and SPSS software version 16. Results: meta-cognitive beliefs as well as the Cognitive-executive functions of brain had a positive relationship with sleep disorders (P<0.001) and the relationship between meta-cognitive beliefs and degree of optic nerve involvement. Conclusion: It can be concluded that the relationship between meta-cognitive beliefs and Cognitive-executive functions of brain، sleep disorders ، optic neuritis in Multiple Sclerosis Patients is not a simple linear one. This is partly mediated by meta-cognitive beliefs deficit.