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重复经颅磁刺激对核黄疸大鼠模型苍白球GABA能神经元及运动功能的影响

Effects of Repetitive Transcranial Magnetic Stimulation on Pallidum GABAergic Neurons and Motor Function in Rat Models of Kernicterus.

作者信息

Wang Nanqin, Jia Yongzhu, Zhou Xuanzi, Wang Xia, Zhou Huyao, Xiao Nong

机构信息

Department of Rehabilitation, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing 400010, China.

出版信息

Brain Sci. 2023 Aug 28;13(9):1252. doi: 10.3390/brainsci13091252.

Abstract

Kernicterus is a serious complication of hyperbilirubinemia, caused by neuronal injury due to excessive unconjugated bilirubin (UCB) in specific brain areas. This injury induced by this accumulation in the globus pallidus can induce severe motor dysfunction. Repetitive transcranial magnetic stimulation (rTMS) has shown neuroprotective effects in various neurological diseases. This study aimed to investigate the effects of rTMS on pallidal nerve damage and motor dysfunction in a rat model of kernicterus. Rats were divided into a sham group (n = 16), a model group (bilirubin with sham rTMS; n = 16) and an rTMS group (bilirubin with rTMS; n = 16). High-frequency rTMS (10 Hz) was applied starting from 24 h postmodeling for 7 days. The rotarod test, western blotting and immunohistochemical staining were performed to measure motor function and protein expression levels. The rTMS mitigated the negative effects of UCB on the general health of kernicterus-model rats and improved their growth and development. Furthermore, the rTMS alleviated UCB-induced motor dysfunction and increased the expression of GABAergic neuronal marker GAD67 in the globus pallidus. Notably, it also inhibited apoptosis-related protein caspase-3 activation. In conclusion, rTMS could alleviate motor dysfunction by inhibiting apoptosis and increasing globus pallidus GAD67 in kernicterus rat models, indicating that it may be a promising treatment for kernicterus.

摘要

核黄疸是高胆红素血症的一种严重并发症,由特定脑区中过量的未结合胆红素(UCB)导致神经元损伤引起。苍白球中这种胆红素的蓄积所导致的损伤可诱发严重的运动功能障碍。重复经颅磁刺激(rTMS)已在多种神经系统疾病中显示出神经保护作用。本研究旨在探讨rTMS对核黄疸大鼠模型中苍白球神经损伤和运动功能障碍的影响。将大鼠分为假手术组(n = 16)、模型组(胆红素加假rTMS;n = 16)和rTMS组(胆红素加rTMS;n = 16)。从建模后24小时开始应用高频rTMS(10 Hz),持续7天。进行转棒试验、蛋白质免疫印迹法和免疫组织化学染色以测量运动功能和蛋白质表达水平。rTMS减轻了UCB对核黄疸模型大鼠总体健康的负面影响,并改善了它们的生长发育。此外,rTMS减轻了UCB诱导的运动功能障碍,并增加了苍白球中γ-氨基丁酸能神经元标志物GAD67的表达。值得注意的是,它还抑制了凋亡相关蛋白半胱天冬酶-3的激活。总之,rTMS可通过抑制凋亡和增加核黄疸大鼠模型苍白球中GAD67的表达来减轻运动功能障碍,表明它可能是一种有前景的核黄疸治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4865/10526431/d27822400547/brainsci-13-01252-g001.jpg

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