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Memory impairment is a critical issue in patients with temporal lobe epilepsy (TLE). Neuronal loss within the hippocampus and recurrent seizures may cause cognitive impairment in TLE. N -acetyl cysteine (NAC) is a sulfur-containing amino acid cysteine that is currently being investigated due to its protective effects on neurodegenerative disorders. NAC was orally administrated at a dose of 100 mg/kg for 8 days (7-day pretreatment and 1-day post-surgery). Neuronal viability, mTOR protein level, and spatial memory were detected in the kainite temporal epilepsy model via Nissl staining, western blot method, and Morris water maze task, respectively. Results showed that NAC delayed seizure activity and ameliorated memory deficit induced by Kainic acid. Histological analysis showed that NAC significantly increased the number of intact neurons in CA3 and hilar areas of the hippocampus following the induction of epilepsy. NAC also modulated the mTOR protein level 5 days after epilepsy compared to the KA-induced group. CONCLUSION: These results suggest that NAC improved memory impairment via anticonvulsant and neuroprotective activity and, in all probability, by lowering the level of mTOR.

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Understanding the underlying molecular mechanisms involved in epilepsy is critical for the development of more effective therapies. It is believed that mTOR (Mechanistic Target of Rapamycin kinases) activity and the mitochondrial dynamic balance change during epilepsy. mTOR affects mitochondrial fission by stimulating the translation of mitochondrial fission process 1 (MTFP1). In This study, the protective role of N-acetylcysteine was studied in temporal lobe epilepsy (TLE) through the regulation of mTOR and mitochondrial dynamic proteins. Rats received N-acetylcysteine (oral administration) seven days before induction of epilepsy, followed by one day after epilepsy. TLE was induced by microinjection of kainite into the left lateral ventricle. The total mTOR and Drp1 levels in the hippocampus were evaluated by western blotting. MFN1 was assessed using immunohistochemistry, and the expression of Fis.1 and MTFP1 (fission-related proteins) and OPA (fusion-related protein) were detected by real-time PCR. The mitochondrial membrane potential was measured by Rhodamin 123. The results showed that 72 h after induction of epilepsy, the mTOR protein level increased, and the balance of the mitochondrial dynamic was disturbed; however, oral administration of NAC decreased the mTOR protein level and improved the mitochondrial dynamic. These findings indicate that NAC plays a neuroprotective role in temporal lobe epilepsy, probably through decreasing the mTOR protein level, which can improve the imbalance in the mitochondrial dynamic.

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INTRODUCTION: Stroke is one of the most common causes of death worldwide. Inflammation and apoptosis play an important role in the cascade of ischemic stroke.

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Introduction: Viola plant has been used traditionally to treat neurological disorders. We aimed at determining whether pretreatment with Viola spathulata extract can alleviate the severity of ischemic-reperfusion damages and exert its protective effects through the regulation of a sodium/calcium exchanger (NCX3) gene expression in a rat brain. Methods: Male Wistar rats were divided into two main groups: one main group for evaluating Neurologic Deficit Score (NDS) and Infarct Volume (IV) and the other group for the evaluation of NCX3 gene expression in the brain tissue. The latter group was subdivided into the intact, control (vehicle), sham, V5, and V10. The vehicle (control) subgroup received Dimethyl Sulfoxide (DMSO), and V5 and V10 subgroups received V. spathulata extract at the doses of 5 and 10 mg/kg (IP), respectively, for 7 days. After pretreatment, we carried out Middle Cerebral Artery Occlusion (MCAO) for 60 min. Results: In the V5 and V10 subgroups, NDS and IV significantly decreased. MCAO upregulated NCX3 gene expression in the core, penumbra, and subcortical regions compared with the intact subgroup. The V5 subgroup significantly downregulated the NCX3 gene expression level in the core compared with the control subgroup. The V10 subgroup showed downregulation of the NCX3 gene expression level in the core, penumbra, and subcortex compared with the control subgroup. Conclusion: V. spathulata extract may have a neuroprotective role against MCAO-induced ischemic brain damage, possibly by preventing the alteration of NCX3 gene expression level. Highlights: MCAO results Infarct Volume (IV) and Neurologic Deficit Score (NDS);MCAO upregulated NCX3 gene expression in brain tissues;Viola spathulata extract pretreatment decreased IV and NDS in brain ischemia;Viola spathulata pretreatment downregulated NCX3 gene expression in brain tissues. Plain Language Summary: Stroke is the second leading cause of death and long term disability. Recently it has been reported that herbal extracts have protective role in ischemia injury. In Iranian traditional medicine Viola plant has a long history to treat disorders such as cancer. So we designed an animal study to investigate Viola plant extract in brain ischemia injury. Viola spathulata extract was administrated to rats for seven days, then animal model of brain ischemia was operated on them and some behavioral, histological and molecular factors were analyzed. Our findings showed that Viola spathulata extract improved behavioral disability, decreased infarct volume in brain tissue, and modulate Sodium/Calcium exchanger 3 gene expression. It could be concluded that Viola spathulata has the neuroprotective effect in animal stroke model and is a good candidate for nutritional supplements, although further studies are needed.

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The new coronavirus has spread throughout the world in a very short time and now has become a pandemic. Most infected people have symptoms such as dry cough, dyspnea, tiredness, and fever. However, the Covid-19 infection disrupts various organs, including the liver, kidney, and nervous system. Common neurological symptoms of the Covid-19 infection include delirium, confusion, headache, and loss of sense of smell and taste. In rare cases it can cause stroke and epilepsy. The virus enters the nervous system either directly through nerve pathways or indirectly through the ACE2 receptor. The neurological symptoms of a Covid-19 infection in the brain are mainly due to either the entry of pro-inflammatory cytokines into the nervous system or the production of these cytokines by microglia and astrocytes. Pro-inflammatory cytokines can cause blood-brain barrier disruption, increase in glutamate and aspartate and reduce GABA levels, impairs the function of ion channels, and finally, high levels of cytokines can cause epilepsy. Understanding the potential mechanisms is necessary to gain better insight into COVID-19 induced seizure pathogenesis and to design the correct treatment strategies to achieve appropriate treatment for seizure and epilepsy.

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BACKGROUND: The purpose of this study was to determine if normobaric hyperoxia (HO) pre-conditioning offers durable neuroprotection against cerebral ischaemia and its effects on NCX1 expression. METHODS: Rats were divided into two experimental groups. The first group was exposed to 95% inspired HO for 4 hours/day for 6 consecutive days (HO). The second group acted as control and was exposed to 21% oxygen in the same chamber. Each main group was sub-divided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) sub-groups. After 2, 5, 10 and 15 days from pre-treatment, MCAO-operated sub-groups were subjected to 60 minutes of right MCAO. After 24 hours reperfusion, neurologic deficit score and infarct volume were measured in MCAO-operated sub-groups. The NCX1 expression levels of core, penumbra and sub-cortex regions were assessed in sham-operated and intact sub-groups. RESULTS: Pre-conditioning with HO decreased neurologic deficit score and infarct volume, and increased expression of NCX1 in penumbra and sub-cortex. These effects of hyperoxia disappeared gradually during 15 days after pre-treatment. CONCLUSIONS: Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO partly is associated with expression of NCX1 consistent with an active role in the genesis of ischaemic neuroprotection.

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