International Journal of Neuroscience最新文献

Background and aim: Monosodium glutamate (MSG) is used in food-additives, and the Food and Drug Administration has placed it under intense scrutiny following several reports that it causes glutamate neurotoxicity. Ashwagandha (ASH) roots are traditionally used for memory enhancement. This study aimed to evaluate the nootropic activity of ASH as well as its therapeutic anti-amnesic activity against MSG-induced hippocampal-dependent spatial memory impairment and hippocampal-NMDAR modulation.

Method: A total of 36 rats were divided equally into six groups (n = 6 in each group); the rats in the normal and negative groups were administered daily doses of normal saline and MSG (300 mg/kg), respectively, for 21 days. Two nootropic groups were administered ASH at 300 and 500 mg/kg o.p., respectively, for 21 days. Two other treatment groups were administered daily doses of MSG 300 mg/kg o.p. as well as 300 mg/kg and 500 mg/kg o.p. of ASH for 21 days. The rats' spatial memory was assessed for five days using the MWM. Additionally, NMDAR were measured quantitatively by immunohistochemistry.

Results: We found that the rats in the nootropic groups showed significantly enhanced nootropic activity characterized by improved hippocampal-dependent spatial memory, as well as increases in the level of NMDAR in the Cornu Ammonis 1 region of their hippocampus. Moreover, we elucidated the therapeutic potential of ASH to protect against the depression of spatial memory caused by MSG-induced neurotoxicity.

Conclusion: Further, we elucidated a strong correlation between NMDAR-positive cells in the hippocampus and enhancement of spatial learning induced by long-term administration of ASH as well as a strong correlation between NMDAR positive cells in the hippocampus and depression of spatial learning induced by long-term administration of ASH and MSG.

Neurodevelopment can be precisely regulated by epigenetic mechanisms, including DNA methylations, noncoding RNAs, and histone modifications. Histone methylation was a reversible modification, catalyzed by histone methyltransferases and demethylases. So far, dozens of histone lysine demethylases (KDMs) have been discovered, and they (members from KDM1 to KDM7 family) are important for neurodevelopment by regulating cellular processes, such as chromatin structure and gene transcription. The role of KDM5C and KDM7B in neural development is particularly important, and mutations in both genes are frequently found in human X-linked mental retardation (XLMR). Functional disorders of specific KDMs, such as KDM1A can lead to the development of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Several KDMs can serve as potential therapeutic targets in the treatment of neurodegenerative diseases. At present, the function of KDMs in neurodegenerative diseases is not fully understood, so more comprehensive and profound studies are needed. Here, the role and mechanism of histone demethylases were summarized in neurodevelopment, and the potential of them was introduced in the treatment of neurodegenerative diseases.

Glioblastoma is the most aggressive type of brain tumor, with current therapies failing to significantly improve patient survival. Vitamins have important effects on cellular processes that are relevant for tumor development and progression.

Aim: The present study explored the effect of pyridoxine or cobalamin supplementation on the viability and cell cycle progression of human glioblastoma cell line U-87 MG.

Method: Cell cultures were treated with increasing concentrations of pyridoxine or cobalamin for 24-72 h. After supplementation, cell viability and cell cycle progression were assessed by spectrophotometry and flow cytometry. Analysis of Bcl-2 and active caspase 3 expression in supplemented cells was performed by western blot.

Result: The results show that pyridoxine supplementation decreases cell viability in a dose and time dependent manner. Loss of viability in pyridoxin-supplemented cells is probably related to less cell cycle progression, higher active caspase 3 expression and apoptosis. In addition, Bcl-2 expression did not appear to be altered by vitamin supplementation, but active caspase 3 expression was significantly increased in pyridoxine-, but not cobalamin-supplemented cells, furthermore, cobalamin inhibited the pyridoxine cytotoxicity in the cell viability assay when combined.

Conclusion: The results suggest that pyridoxine supplementation promotes apoptosis in human glioblastoma-derived cells and may be useful to enhance the effect of cytotoxic therapies in vivo.

Purpose: Inappropriate inflammatory responses within the nervous system (neuroinflammation) have been implicated in several neurological conditions. Class II transactivator (CIITA), a principal regulator of the major histocompatibility complex II (MHCII), is known to play essential roles in inflammation. Hence, CIITA and its interactors could be potentially involved in multiple neurological disorders. However, the molecular mechanisms underlying CIITA-mediated neuroinflammation (NI) are yet to be understood.

Materials and methods: In this regard, we analyzed the potential involvement of CIITA and its interactome in the regulation of neuroinflammation. In the present study, using various computational tools, we aimed (1) to identify NI-related proteins, (2) to filter the critical interactors in the CIITA-NI network, and (3) to analyze the protein-disease interactions and the associated molecular pathways through which CIITA could influence neuroinflammation.

Results: CIITA was found to interact with P T GS2, GSK3B, and NR3C1 and may influence depressive disorders. Further, the IL4/IL13 pathway was found to be potentially underlying the CIITA-interactomemediated effects on neurological disorders. Moreover, CIITA was found to be connected to genes associated with depressive disorder through IL4, wherein CIITA was found to be potentially involved in depressive disorders through IL-4/IL-13 and hippo pathways. However, the present study is based on the existing data on protein interactomes and could be re-evaluated as newer interactions are discovered. Also, the functional mechanisms of CIITA's roles in neuroinflammation must be evaluated further.

Conclusion: Notwithstanding these limitations, the results presented here, could form a basis for further experimental studies to assess CIITA as a potential therapeutic target in managing depression and other neuroinflammatory disorders.

Studies have shown that neurodegenerative diseases such as AD and PD are related to neuroinflammation. Neuroinflammation is a common inflammatory condition that can lead to a variety of dysfunction in the body. At present, it is no medications specifically approved to prevent or cure neuroinflammation, so even though many drugs can temporarily control the neurological symptoms of neuroinflammation, but no one can reverse the progress of neuroinflammation, let al.one completely cure neuroinflammation. Therefore, it is urgent to develop new drug development for neuroinflammation treatment. In this review, we highlight the therapeutic advancement in the field of neurodegenerative disorders, by focusing on the impact of neuroinflammation treatment has on these conditions, and the effective drugs for the treatment of neuroinflammation and neurodegenerative diseases and their latest research progress are reviewed according to the related signaling pathway, as well as the prospect of their clinical application is also discussed. The purpose of this review is to enable specialists to better understand the mechanisms underlying neuroinflammation and anti-inflammatory drugs, promote the development of therapeutic drugs for neuroinflammation and neurodegenerative diseases, and further provide therapeutic references for clinical neurologists.

Introduction: Intravenous thrombolytic therapy (IVTT) is licensed for patients under 80 years in many countries. In this study, we aimed to demonstrate functional results and complication rates of IVTT in patients over eighty years and whether there is a difference in efficacy and safety between low dose and standard dose recombinant tissue plasminogen activator (rTPA).

Methods: A retrospective observational study of patients over eighty who admitted to Suleyman Demirel University Faculty of Medicine Hospital between August 2016 and April 2021 and to Isparta City Hospital between April 2017 and April 2021 and diagnosed with acute ischemic stroke were conducted. Third month modified rankin scores (mRS) and mortality rates of patients and hemorrhagic transformations were determined.

Results: There were 29 patients in IVTT group and 25 patients in non-IVTT group. By the third month, it was observed that functional independence (mRS 0-2) ratio was increased more in IVTT group, but it wasn't statistically significant (p: 0.087). In mortality and symptomatic intracerebral hemorrhage rates, there wasn't statistically significant difference between IVTT and non-IVTT groups and low dose and standard dose rTPA groups by the third month.

Conclusion: The efficacy and complication rates of IVTT in patients over 80 years were found similar to not receive IVTT. These results support the safety of IVTT in patients over 80 years. In low or standard dose rTPA preference, we observed that there was not statistically significance in efficacy and safety. We believe that these results will be supported by studies with larger number of patients.

Background: Extracranial internal carotid aneurysms consist a rare pathology with an overall incidence less than 1% in the general population, and warrant treatment due to their association with cerebrovascular events and neurological complications. The incidence is even lower in the pediatric population.

Case report: A 14-month infant presented in our clinic with neck swelling of unknown origin, with subsequent MR imaging revealing an extracranial internal carotid aneurysm. Due to the patient's age and risk of surgical complications, the decision to proceed with endovascular repair with stent placement and complete exclusion of the aneurysm from the circulation was made, after multidisciplinary consultation.

Results: In the pediatric population, pediatric population, endovascular stent placement can be considered at least as a last resort treatment when surgical access harbors significant risks or is impossible.

Genetic vulnerability contributes significantly to the individual variability observed in nicotine dependence. Selective breeding for sensitivity to a particular effect of abused drugs has produced rodent lines useful for studying genetic vulnerability to drug addiction. Previous research showed that anxiety-related personality traits are associated with nicotine dependence. Therefore, we examined the differences in anxiety-like behavior between a high nicotine-preferring rat line and their controls. At the beginning of the study, all rats, naïve to any drug, were exposed sequentially to open field arena, marble-burying and elevated plus-maze paradigms. In the second step, all rats received nicotine in drinking water for 7 weeks. Behavioral tests were rerun on the final 2 weeks of chronic nicotine treatment. Elevated plus-maze testings under basal condition and during chronic nicotine treatment showed that the time spent on the open arms, preference for being in the open arms, and the latency to enter the closed arms were higher, whereas open arm avoidance index was lower in nicotine-preferring rats compared to the controls. In the open field test, nicotine-preferring rats spent longer time in the central zone and excreted less fecal pellets; they buried less marbles in the marble-burying test. These findings indicate a lower level of anxiety-like behavior in nicotine-preferring rat line under basal conditions and during chronic nicotine treatment. We conclude that lower anxiety level in nicotine-preferring rat line is consistent with novelty-seeking personality type and may increase vulnerability to nicotine dependence in this rat line.

Purpose: Muscle activation often occurs in muscles ipsilateral to a voluntarily activated muscle and to a greater extent after stroke. In this study, we measured muscle activation in non-target, ipsilateral leg muscles and used transcranial magnetic stimulation (TMS) to provide insight into whether corticomotor pathways contribute to involuntary activation.

Materials and methods: Individuals with stroke performed unilateral isometric ankle dorsiflexion, ankle plantarflexion, knee extension, and knee flexion. To quantify involuntary muscle activation in non-target muscles, muscle activation was measured during contractions from the ipsilateral tibialis anterior (TA), medial gastrocnemius (MG), rectus femoris (RF), and biceps femoris (BF) and normalized to resting muscle activity. To provide insight into mechanisms of involuntary non-target muscle activation, TMS was applied to the contralateral hemisphere, and motor evoked potentials (MEPs) were recorded.

Results: We found significant muscle activation in nearly every non-target muscle during isometric unilateral contractions. MEPs were frequently observed in non-target muscles, but greater non-target MEP amplitude was not associated with greater non-target muscle activation.

Conclusions: Our results suggest that non-target muscle activation occurs frequently in individuals with chronic stroke. The lack of association between non-target TMS responses and non-target muscle activation suggests that non-target muscle activation may have a subcortical or spinal origin. Non-target muscle activation has important clinical implications because it may impair torque production, out-of-synergy movement, and muscle activation timing.

Purpose: Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017-August 2025) in all patients in Japan who were administered nusinersen intrathecally in real-world clinical settings. We report the interim analysis results for safety and effectiveness.

Methods: This interim analysis was conducted using data collected from 524 patients whose case report forms were obtained at least once by May 30, 2022. Collected data included patient demographics and adverse events (AEs) for safety, and motor function assessments and Clinical Global Impressions of Improvement (CGI-I) for effectiveness.

Results: Of the 524 patients in the safety analysis set, 522 patients who were diagnosed with SMA were included in the effectiveness analysis (infantile-onset SMA [n = 153, 29.3%], later-onset SMA [n = 369, 70.7%]). The median duration of treatment was 785.0 (range 1-1549) days. AEs occurred in 35.9% of patients (49.0% in infantile-onset SMA and 30.6% in later-onset SMA). Nusinersen treatment significantly improved Hammersmith Infant Neurological Examination scores in patients with infantile-onset SMA and Hammersmith Functional Motor Scale-Expanded scores in patients with later-onset SMA for up to nearly 3 years. Based on CGI-I assessments, 98.5-100% of patients receiving nusinersen 'improved' or remain 'unchanged'.

Conclusions: This interim analysis of the large-scale, all-case PMS in patients who were administered nusinersen in Japan supports the safety and effectiveness of nusinersen. The benefit-risk balance of nusinersen treatment remains favorable.