rTMS ameliorates cerebral ischemia-reperfusion injury by inhibiting Golgi apparatus stress through epigenetic modulation of Gli2.

Cerebral ischemic stroke represents a primary cause of permanent disability and mortality globally. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a prominent focus in treating a wide range of neurological disorders. In this study, we explore the role of rTMS in alleviating cerebral ischemia-reperfusion (I/R) injury by mediating Golgi apparatus (GA) stress. Here, we find that rTMS upregulates Dram1 expression and ameliorates GA stress in cerebral I/R injury in vivo and in vitro. Gli2 transcriptionally activates Dram1. HDAC5 inhibits H3K27ac modification of Gli2 promoter. rTMS promotes Gli2 expression by inhibiting HDAC5. Gli2 knockdown reverses the inhibitory effect of rTMS on OGD/R-induced neuronal GA stress. In conclusion, rTMS inhibits HDAC5-mediated deacetylation of Gli2 promoter to promote the transcriptional activation of Dram1, thereby suppressing cerebral I/R-induced GA stress. Targeting Gli2/ Dram1 axis may be an effective way to enhance the anti-ischemic stroke effect of rTMS.