Repetitive transcranial magnetic stimulation (rTMS) is acknowledged as a form of neurostimulation, especially for functional recovery. The foundational knowledge of molecular mechanism is limited regarding its role in cerebral ischemia, for which the present study was designed. Primary neurons were treated with oxygen-glucose deprivation (OGD) and repetitive magnetic stimulation (rMS), in which brain-derived neurotrophic factor (BDNF) and transcription of BDNF exons were examined. Then, adenovirus vectors carrying siRACK1 sequence were delivered to primary neurons, followed by detection of the transcription of BDNF exons and the extent of methyl CpG binding protein 2 (MeCP2) phosphorylation. Results showed that BDNF and the transcription of BDNF exons were upregulated by rMS and OGD treatment, but decreased by extra treatment of RACK1 siRNA. Then, the mechanism investigations demonstrated that rMS increased the extent of MeCP2 phosphorylation to promote the interaction between RACK1 and BDNF exon IV. The aforementioned findings were further confirmed in vivo in middle cerebral artery occlusion (MCAO)-induced rat models, as indicated by improved neurological functions and reduced area of cerebral infarction. The study offers potential evidence for improvement of neurological deficits, highlighting the important role of rTMS for treatment of cerebral ischemia.

中文翻译：

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重复经颅磁刺激通过磷酸化依赖性因子 MeCP2 与 RACK1 和 BDNF 外显子 IV 之间的相互作用来缓解脑缺血后的神经缺陷。


重复经颅磁刺激（rTMS）被认为是神经刺激的一种形式，特别是对于功能恢复。关于其在脑缺血中的作用的分子机制的基础知识是有限的，而本研究正是为此而设计的。原代神经元接受氧糖剥夺（OGD）和重复磁刺激（rMS）治疗，其中检查脑源性神经营养因子（BDNF）和BDNF外显子的转录。然后，将携带siRACK1序列的腺病毒载体递送至原代神经元，检测BDNF外显子的转录和甲基CpG结合蛋白2（MeCP2）磷酸化的程度。结果显示，rMS和OGD处理使BDNF和BDNF外显子的转录上调，但通过RACK1 siRNA的额外处理而下调。然后，机制研究表明rMS增加了MeCP2磷酸化的程度，从而促进RACK1和BDNF外显子IV之间的相互作用。上述发现在大脑中动脉闭塞（MCAO）诱导的大鼠模型中得到进一步证实，神经功能改善和脑梗塞面积减少表明。该研究为改善神经功能缺损提供了潜在的证据，强调了 rTMS 在治疗脑缺血方面的重要作用。