Zhang Haofuzi, Yang Yuefan, Yang Erwan, Tian Zhicheng, Huang Yutao, Zhang Zhuoyuan, Bao Mingdong, Liao Dan, Ge Junmiao, Wang Chao, Li Xin, Luo Peng
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 12769 Changle Xi Road, Xi'an, 710032, China.
Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.
Cell Mol Neurobiol. 2023 Apr;43(3):1301-1317. doi: 10.1007/s10571-022-01251-2. Epub 2022 Jul 13.
Neuroinflammation is one of the most important pathological processes following brain ischemia. Pulsed electromagnetic fields (PEMFs) protect against brain ischemia, but their role in regulating neuroinflammation remains unclear. In the present study, we investigated the biological effects of PEMF exposure on brain ischemia-induced neuroinflammation through the astrocytic cholinergic anti-inflammatory pathway. PEMF exposure reduced the activation of astrocytes and neuroinflammation following brain ischemia by directly modulating astrocytic injury and inflammatory cytokine release. Inhibition of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) by a specific antagonist reversed the regulatory effects of PEMF on astrocytes. Furthermore, negative regulation of signal transducer and activator of transcription 3 (STAT3) by α7nAChR was found to be an important downstream mechanism through which PEMF regulates astrocyte-related neuroinflammation. PEMF suppressed STAT3 phosphorylation and nuclear translocation by activating α7nAChR. These results demonstrate that PEMF exerts anti-inflammatory effects in the context of brain ischemia by modulating astrocytic α7nAChR/STAT3 signaling.
神经炎症是脑缺血后最重要的病理过程之一。脉冲电磁场(PEMFs)可预防脑缺血,但其在调节神经炎症中的作用仍不清楚。在本研究中,我们通过星形胶质细胞胆碱能抗炎途径研究了PEMF暴露对脑缺血诱导的神经炎症的生物学效应。PEMF暴露通过直接调节星形胶质细胞损伤和炎症细胞因子释放,减少了脑缺血后星形胶质细胞的活化和神经炎症。特异性拮抗剂对烟碱型乙酰胆碱受体α7亚基(α7nAChR)的抑制作用逆转了PEMF对星形胶质细胞的调节作用。此外,发现α7nAChR对信号转导和转录激活因子3(STAT3)的负调控是PEMF调节星形胶质细胞相关神经炎症的重要下游机制。PEMF通过激活α7nAChR抑制STAT3磷酸化和核转位。这些结果表明,PEMF通过调节星形胶质细胞α7nAChR/STAT3信号通路在脑缺血情况下发挥抗炎作用。