Inflammatory mechanism of COP1‑mediated low‑frequency repetitive transcranial magnetic stimulation in the treatment of epilepsy

Objective The present study sought to uncover the underlying molecular mechanisms of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in epilepsy treatment. Methods In BV2 cells and status epilepticus (SE) mice, COP1 expression was manipulated by molecular approaches, and then LF-rTMS was applied. Then real time quantitative PCR, Western Blot, Immunofluorescence Staining and Elisa were performed. Results We observed that COP1 expression was markedly decreased in the hippocampus and microglia of SE mice. In vitro experiments revealed that overexpression of COP1 (OE-COP1) notably reduced PILO-induced microglial activation as assessed by IBA1 expression. In vivo, OE-COP1 alleviated oxidative stress and downregulated pro-inflammatory cytokines in SE mice. Moreover, LF-rTMS treatment notably increased COP1 expression and inhibited C/EBPβ expression in the hippocampus of SE mice; knockdown of COP1 (sh-COP1) abolished these effects. Further validation demonstrated that LF-rTMS reduced microglial activation, oxidative stress, and pro-inflammatory cytokine levels in SE mice by promoting COP1 expression. Conclusions Our findings identify COP1 as a key mediator through which LF-rTMS exerts its therapeutic effects in epilepsy treatment, namely by upregulating COP1 to inhibit neuroinflammation and oxidative stress. This study establishes a novel molecular basis for applying LF-rTMS clinically in epilepsy.