High-frequency rTMS attenuates cerebral ischemia/reperfusion injury and modulates mTOR-related signaling and brain-gut-immune phenotypes in MCAO/R rats.
Abstract
Background
High-frequency repetitive transcranial magnetic stimulation (rTMS) may promote neurological recovery after ischemic stroke, but its protective effects after MCAO/R and associations with neurotrophic factors, mTOR-related autophagy markers, systemic inflammation, and gut microbiota phenotypes remain unclear.
Methods
Cerebral ischemia/reperfusion injury was induced by right MCAO/R. Rats were assigned to Sham, MCAO/R, and MCAO/R + high-frequency rTMS groups. rTMS was initiated on postoperative day 3. Neurological and motor functions were assessed behaviorally. Western blotting, immunofluorescence, ELISA, and 16S rRNA sequencing were used to examine related proteins, inflammatory cytokines, and gut microbiota, followed by multivariate and correlation analyses.
Results
High-frequency rTMS improved neurological and motor functions, reduced infarction and histopathological injury, decreased TUNEL positivity, and increased the number of Nissl-positive neurons. It upregulated FGF-2, BDNF, and the p-mTOR (Ser2448)/mTOR ratio, attenuated abnormal changes in Beclin-1, LC3-II/LC3-I, and p62, and reduced serum TNF-α, IL-1β, and IL-6 levels. 16S rRNA sequencing showed altered gut microbiota β-diversity and genus-level composition, with several genera associated with motor or inflammatory indices.
Conclusion
High-frequency rTMS alleviated cerebral ischemia/reperfusion injury and promoted neurological recovery after MCAO/R, accompanied by enhanced neurotrophic support, improvement in mTOR-related autophagy marker abnormalities, and lower serum pro-inflammatory cytokine levels. Gut microbiota alterations were also observed following rTMS treatment, although their functional significance remains exploratory.