Neurology and Neurological Disorders

Ayman ElAli has completed his PhD in 2010 at the University of Duisburg-Essen in Germany. He pursued his Post-doctoral trainings at the research centres of University Hospital of Essen in Germany, and CHU de Québec in Canada. He joined in 2015 the Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Canada, as an Assistant Professor. His research program aims at Investigating Neurovascular Interactions Following Stroke with an Emphasis on Developing New Therapeutic Approaches. He has published more than 37 papers in top-tier journals and has been serving as Referee in several reputed funding organizations and journals.

Ischemic stroke constitute a major cause of death and disability of the adults in the world. Unfortunately, no efficient therapy does yet exist. Endogenous neurovascular restorative responses are triggered within the ischemic tissue, as an attempt from the brain to recover. Ischemic stroke triggers the formation of new microvasculature in the peri-infarct region via activation of various angiogenic mechanisms. Neuronal survival is higher in the tissue undergoing angiogenesis, correlating with longer survival in stroke patients. Angiogenesis is a highly dynamic process that involves close and finely tuned interactions between brain endothelial cells and pericytes. Pericytes play major roles in regulating the cerebral blood flow, angiogenesis, microvasculature stability, and blood-brain barrier (BBB) properties. Ischemic stroke profoundly affects the function of pericytes by triggering their death and detachment from brain endothelial cells, which impairs key neurovascular functions within the ischemic tissue. Using in vivo and in vitro approaches, our recent work demonstrates that vascular endothelial growth factor isoform-B (VEGF-B), which acts as survival factor, promotes the formation of stable microvasculature within the ischemic tissue by specifically enhancing the survival of pericytes and their interaction with brain endothelial cells. We found that the effects of VEGF-B are mediated via its specific receptor VEGFR-1 that is predominately expressed in brain pericytes. Our study unravelled an unknown role of VEGF-B/VEGFR-1 signalling in rescuing the function of pericytes by inducing expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2) and AMP-activated protein kinase α (AMPKα) protein, which is involved in energy homeostasis. Moreover, VEGF-B/VEGFR-1 signalling stimulates the release of factors stimulating a reparative angiogenesis that does not compromise microvasculature stability and BBB permeability. Our findings suggest that strategies aiming to stimulate the endothelial cell-pericyte crosstalk constitute a promising therapeutic approach to promote neurovascular repair upon ischemic stroke. \r\n\r\n

Tuychibaeva NM is an Assistant Professor, Neurologist at Tashkent Medical Academy, depart-ment of Neurology and Intermed Clinic City Child Diagnostics Center respectively. She has completed her Bachelor’s degree (1990-1996) and Clinical Fellowship in Adult Neurology (1996-1999) at Tashkent Medical Academy, Uzbekistan. She obtained her PhD in Medicine (March 29, 2007) on Clinical features of Consequence of light cerebral trauma from Second Tashkent State Medical Institute. She has done training courses on epilepsy, pediatric related topics. The main fields of her clinical researches are neurology and medical genetics. She has an expertise in epi-lepsy, but now she is also interested in different movement disorders, especially in childhood.

Background: Antiepileptic drugs (AED) considered to be the most effective method of treat-ment of epilepsy, but they are not only ineffective in pharmacoresistant forms, but also can make patient’s condition more severe. It forced us to risk and at the first time in Uzbekistan tries to use ketogenic diet in patients with epilepsy.\r\n\r\nMaterials & Methods: We investigated the duration of pharmacoresistant epilepsy in 7 children of Uzbek nationality aged from 2 to 9 at the first time when treated by AED, then by glucocorti-coids and after the cancellation of drugs and use only classic ketogenic diet. All of them were under the clinical examination with use of MRI, EEG with video monitoring, and USD of liver and gallbladder, ketone and glucose tests. In children 3 used only glucocorticoids; in 4 children we used combination of hydrocortisone in dose 5 mg/kg and AED. Proven ineffectiveness of AED and glucocorticoids allowed us to prescribe them ketogenic diet with macronutrient ratio 4:1 that was counted by ketocalculator. Every week parents provided ketone bodies analyses in urine and measured glucose level in blood of children. Once a 3 months was performed blood analysis by gas analyzer.\r\n\r\nResults: In all children on EEG was noted decreased epileptiform activity, but much better re-sults were in patients without MRI changes. Convulsions were under the control, there almost were not generalized seizures in patients with Lennox-Gastaut, West and Landau-Kleffner syn-dromes. Cognitive functions, when their impairment was the main symptom, also partially re-turned and there was observed significant progress in psychical development and social adapta-tion of children. There were no any cases of hypoglycemic coma.\r\n\r\nConclusion: Ketogenic diet if followed correctly may significantly improve the condition of pa-tients with pharmacoresistant forms of epilepsy. \r\n

Zahida Taibi-Djennah has completed her PhD in Biochemistry-Immunology and Innovative Biotherapies from University of Sciences and Technology Houari Boumdiene, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology. She is an Associate Professor level B at University of Sciences and Technology Houari and is team member of Biochemistry of Biomolecules: Mode of Action, Immunotherapy and Immunodiagnosi (http://www.lbcm.usthb.dz/spip.php?rubrique4). She has published 5 papers in reputed journals including Systemic Responses following Brain Injuries and Inflammatory Process Activation Induced by a Neurotoxin of Androctonus Scorpion Venom in the Journal of Neuroimmunomodulation and Effect of cytokine antibodies in the immunomodulation of inflammatory response and metabolic disorders induced by scorpion venom in the Journal of International Immunopharmacology.\r\n\r\n

Voltage-dependent potassium channels (Kv1.3), play key role in a wide variety of physiological processes, including immunity, metabolism and the stabilization of the resting potential. In brain, activation of insulin receptor is able to induce current suppression coupled to tyrosine phosphorylation of Kv1.3 channel. Moreover, insulin can reduce the production of free radicals and attenuate the inflammatory response. The Kv1.3 channel blockers, such as neurotoxins isolated from scorpion venom, are able to alter neuronal excitability leading to neurological disorders accompanied by inflammatory response. The aim of this study is to evaluate the neuroprotective effect of insulin injected by intra-cerebro-ventricular (i.c.v.) route on neuro-inflammatory response and oxidative stress induced by a blocker of Kv1.3 channel. The ability of insulin to reduce the brain injuries, inflammatory response and oxidative stress biomarkers induced by Kv1.3 channel blocker were assessed in NMRI mice at 24 h after co-injection of insulin and neurotoxin active on potassium channel. Obtained results revealed that the central administration of insulin prevents cerebral cortex injury, brain edema, cells infiltration and a change in the permeability of the blood–brain barrier induced by the Kv1.3 channel blocker. Insulin seems to also reduce significantly the pro-inflammatory cytokines (IL-6, IL-17, TNF-α), MMP-2 and MMP-9 activities and oxidative stress markers (H2O2, NO, MDA) in brain homogenates compared to those observed when animals were injected with Kv1.3 channel blocker alone. These results indicate that insulin is able to modulate the activity of potassium channels in brain by modifying their properties, which probably prevent the binding of neurotoxin to its receptor Kv channel and thus reduce the neuro-pathophysiological effects.

Kadyrkhodjayeva Nigora has finished her study at the Tashkent Medical Academy in 2006. After that, she was studying Psychiatry and Psychotherapeutics from 2006 till 2007 at the Tashkent Institute of Postgraduate Medical Education. She was trained in Neurology at the Tashkent Institute of Postgraduate Medical Education 2007-2009. She has been practicing as a Neurologist since 2009. She passed Clinical attachment in Neurology Department of Rashid Hospital, Dubai, UAE. She has valid practice license from UAE. She successfully cleared certification course of BLS & ACLS in 2018. From September 2017, she is pursuing her PhD at the Tashkent Medical Academy. She has published 3 articles in reputed journals and several articles, abstracts in local journals.

Aim: The aim of the study was to review the quality of life of the patients with daily chronic headache (CDH) and determine the effectiveness of Botulinum toxin type A (BTA) influence on improving the quality of life by reducing the daily headache. \r\n\r\nMaterial & Methods: 54 patients, from both sexes, with a minimum age of 18 years old were studied. The inclusion criteria were the presence of primary daily chronic headache with more than 4-hour duration, a frequency of 15 days or more monthly, in the last three months and disease duration of 3 years for the treatment of CDH using BTA. The study involved 54 patients, of whom where 31 women and 23 men with an average age of 42 years. The patient’s condition was evaluated on the third day, on the 7th day and on the 15th day after the BTA injection and assessed every 15 days for 3 months. The efficacy of BTA was evaluated by several measurements of VAS (Visual Analog Scale), Headache Intake Questionnaire: HSQoLQ (Headache Specific Quality of Life Questionnaire), HMQ (Headache Management Questionnaire), HDQ (Headache Disability Questionnaire). \r\n\r\nResults: After 3 months 2 (4%) patients had no changes, 7 (13%) patients with less than 50 percent reduction in pain, 23 (43%) reported 70 to 95 percent pain relief, and 22 (40%) had complete relief. \r\n\r\nConclusion: The work presented here has profound implications for future studies of BTA injections for patients with CDH. The obtained results testify to an improvement in the quality of life of patients with CDH against the background of injections of BTA. \r\n

Gislei Frota Aragao is graduated in Pharmacy, with Masters and PhD in Pharmacology with a focus on neuropharmacology. Professor of Medical Course at the State University of Ceará (UECE/Brazil) and He is coordinator of the Group of Studies in Neuroinflammation and Neurotoxicology (GENIT). Pharmacist of the Federal University of Ceara (UFC) acting in the Clinical Pharmacology Unit and as a researcher in the laboratory of toxicology and clinical exams in the Drug Research and Development Center (NPDM) with collaborations in the professional Master of Clinical Pharmacology/UFC, Master of Transplantation/UECE and Specialization in Collective Health/UECE, developing projects in the area of neuropharmacology, neurotoxicology, neuroinflammation and pharmacovigilance.

Autism spectrum disorder (ASD) is a neurological and developmental disorder that begins early in childhood and lasts throughout a person\'s life. ASD is characterized by impairment in interaction and social communication, in addition to pro-inflammatory cytokine imbalances with chronic neuroinflammation. Environmental exposures may increase the risk of ASD. There are evidences that as the residue crosses the blood-brain barrier and placenta the fetuses can be exposed to pesticides. The purpose of this study is to summarize and discuss the relationship between autism spectrum disorder and chlorpyrifos, an organophosphate insecticide. The narrative review was performed using MEDLINE, LILACS, Web of Science, Scopus and Science Direct as databases and pesticides, agrochemicals, insecticides, herbicides, Autism disorder as descriptors. Gestational contact with chlorpyrifos interferes early neuromotor development and causes deficits in social behaviour that can lead to long-term deficits in behaviour and repetitive behaviour, as a routine preference. Studies have shown that the contact of chlorpyrifos with already autistic rats increased the characteristics of this disorder in the animals. In addition, contact with chlorpyrifos causes redox imbalance, oxidative stress, mitochondrial dysfunction associated with glutathione deficiency. Studies have also shown that there is a high probability of developing imbalances in the intestinal flora. Autistic individuals may as well exhibit proinflammatory cytokine imbalances and may suffer from hyperactive or dysfunctional immune systems, with chronic neuroinflammation, including neuroglial activation in the brain, and the presence of autoantibodies to brain proteins. Thus, we can conclude that exposures to agricultural pesticides such as chlorpyrifos, through the uterine pathway are related to autism and that there is strong evidence that contact with pesticides may influence the development of autism spectrum disorder.

Tatiana Paschoalette Rodrigues Bachur is a Pharmacist, graduated from the Pharmaceutical Sciences Course of the Federal University of Ceará (UFC-1999) and has completed her Masters in Pathology from the Federal University of Ceara (UFC-2007). She is a Professor of the Medicine Course of the State University of Ceara - UECE, Brazil, Coordinator of specialization courses in the distance learnig modality and collaborates in the Group of Studies in Neuroinflammation and Neurotoxicology – GENIT from UECE. She develops studies in Toxicology, Pharmacology and Tropical Diseases and is a reviewer of scientific journals and project leader.

Sleep disorders have a variable spectrum and are present in all forms of dementia, especially in Alzheimer\'s disease (AD). Elderly patients generally present with sleep disturbances, but this association is more frequent in patients with AD. The aim of this work was to perform a narrative review on the alterations in sleep that occur in patients with AD. A literature review was conducted using MEDLINE, LILACS, Web of Science, Scopus, Science Direct as databases and Alzheimer disease, sleep wake disorders, dyssonias as descriptors. It has been observed that sleep disorders are framed as one of the symptoms of AD, in addition to being related to physiological and genetic patterns. The main symptoms are getting up at night and waking up at night thinking it is day. The incidence of these symptoms was detected in patients with worse cognitive and functional status, lower socioeconomic status and depression. The relationship between insomnia, aggression, paranoid delusions and anxiety was observed. Recent studies have seek to clarify the etiology of sleep disorders, considering associations between absence of healthy sleep with greater deposition of amyloid load in brain regions such as angular gyration, frontal medial orbital cortex, cingulate gyrus and precuneus. Disorders of orexin levels in the cerebrospinal fluid in patients with AD were observed, promoting a change in the activation of the Wake-active monoaminergic system and the deactivation of the REM-on cholinergic groups, reducing sleep homeostasis. Lower body temperature at the end of the day causes disorders of the circadian rhythms in AD and a deficiency in the negative regulation of the proximal blood flow of the daytime skin has been found which may also affect the process. These researches initiate the development of new treatments, which will impact the patient\'s cognition and, consequently, their quality of life. We conclude, therefore, that the sleep disorders are one of the fundamental clinical aspects that must be evaluated in AD patients, specially due to its role as a prognostic changer for the disease.

Edna Maria Camelo Chaves finished her doctorate at the Federal University of Ceará, in Pharmacology. She is an Adjunct Professor at the State University of Ceara, working in the Graduate Program in Physiology and Nursing. She has published more than 13 articles in renowned magazines and has served as a reviewer of scientific journals.

Plant polysaccharides present some activities involving the central nervous system, such as neuroprotective, antidepressant, antioxidant and anti-inflammatory. We aim to evaluate the anticonvulsant and anti-inflammatory effects of the polysaccharide rich extract from G. americana leaves in mice. The leaf dry powder (5 g) was depigmented in methanol and the polysaccharide-rich extract (PRE) obtained by extraction with NaOH followed of precipitation in absolute ethanol. PRE was dissolved in 0.9% NaCl and administered (9 mg/kg) in male Swiss mice (25-35 g) by intraperitoneal (i.p.) route, 30 min before seizures induced by a single dose of pentylenetetrazole (PTZ: 70 mg/kg, i.p), n=7/group. The synergism of PRE effect was evaluated by its association with diazepam (DZP: 0.01 mg/kg). After euthanasia, the prefrontal cortex (CPF), hippocampus (HC) and striatum (EC) were removed for the quantification of myeloperoxidase levels (MPO) by o-dianisidine method. Experimental protocol was approved by Animal Ethics Committee (UECE Nº 2451142/2014). The PRE increased the seizure latency (9 mg/kg: 171,7 ± 29,62 versus saline: 62.00 ± 4,709 s) and death latency (9 mg/kg: 597.4 ± 101,5 versus saline: 150.0 ± 14.52). The association of PRE with diazepam potentiated the protective effect of DZP, increasing seizure latency (DZP: 128,3 ± 24,62 versus PRE + DZP: 222.4 ± 47.57), without altering in death latency. MPO levels was reduced in hippocampus (PRE: 34.24 ± 7.167, DZP: 42.27 ± 9.559 and DZP + PRE: 31.26 ± 5.726 versus saline + PTZ: 81.91 ± 11.70) and striatum (PRE: 17,89 ± 3,310, DZP + PRE: 18.69 ± 3.776 versus saline + PTZ: 37.27 ± 5.169). However there was no difference between groups (DZP, PRE or DZP + PRE) in each brain area. We conclude that PRE of G. americana leaves protects against seizures and promote anti-inflammatory effects in brain. \r\n