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

• Published in: Journal of neuroinflammation 2024-11, Vol.21 (1), p.311-25
• Main Authors: Cheng, Shimei, Lu, Qiying, Liu, Qiuli, Ma, Yuanchen, Chen, Jinshuo, Lu, Di, Huang, Mudan, Huang, Yinong, Zhao, Erming, Luo, Jing, Zheng, Haiqing
• Format: Article
• Language: English
• Subjects: Animals; Brain Ischemia - therapy; Care and treatment; Cell death; Cerebral ischemia; Combined modality therapies; Combined Modality Therapy - methods; Health aspects; Humans; Infarction, Middle Cerebral Artery - therapy; Inflammation; Magnetic brain stimulation; Male; Medical research; Medicine, Experimental; Mesenchymal Stem Cell Transplantation - methods; Neuroinflammation; Neuroinflammatory Diseases - etiology; Neuroinflammatory Diseases - therapy; PANoptosis; Physiological aspects; Programmed cell death; Rats; Rats, Sprague-Dawley; Stem cells; Stroke; Transcranial Magnetic Stimulation - methods; Transplantation
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-024-03302-5

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. 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 molecular mechanisms underlying the special role of rTMS in the combined therapy were distinguished with transcriptome sequencing via PC12 cells in oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. The combined therapy efficiently reduced lesion volume and improved neuronal survival (P