Synergistic effects of repeated transcranial magnetic stimulation and mesenchymal stem cells transplantation on alleviating neuroinflammation and PANoptosis in cerebral ischemia

作者：Shimei Cheng, Qiying Lu, Qiuli Liu, Yuanchen Ma, Jinshuo Chen, Di Lu, Mudan Huang, Yinong Huang, Erming Zhao, Jing Luo, Haiqing Zheng · 发表于：Journal of Neuroinflammation · 年份：2024 · DOI：10.1186/s12974-024-03302-5 · 被引用次数：20 · 研究领域：Mesenchymal stem cell research、Transcranial Magnetic Stimulation Studies、Spinal Cord Injury Research

BACKGROUND: Neuronal death is the primary cause of poor outcomes in cerebral ischemia. The inflammatory infiltration in the early phase of ischemic stroke plays a vital role in triggering neuronal death. Either transplantation of mesenchymal stem cells (MSCs) derived from humans or repetitive transcranial magnetic stimulation (rTMS) have respectively proved to be neuroprotective and anti-inflammatory in cerebral ischemia. However, either treatment above has its limitations. Whether these two therapies have synergistic effects on improving neurological function and the underlying mechanisms remains unclear. This investigation aims to elucidate the synergistic effects and underlying mechanisms of MSCs combined with rTMS treatment on the neurological function recovery post-ischemia. METHODS: A Sprague-Dawley rat model of cerebral infarction was induced via transient middle cerebral artery occlusion (tMCAO). The rats were divided into five groups (n = 50): sham, tMCAO, rTMS, MSCs, and MSCs + rTMS groups. Transplantation of human umbilical cord MSCs and rTMS intervention were performed 24 h post-stroke. Neurological function was further assessed via several behavioral tests and the 2,3,5-triphenyltetrazolium chloride (TTC) staining companied with Nissl staining were used to assess neuronal survival. TUNEL staining, western blotting, immunofluorescence, immunohistochemistry, ELISA, and flow cytometry were employed to measure the levels of neuroinflammation and PANoptosis. The molec...