Transcranial magnetic stimulation alleviates cognitive dysfunction after stroke by inhibiting microglial transformation

• iTBS can alleviate cognitive dysfunction in stroke rats. • iTBS inhibits the MAPK pathway and reduces p-JNK and p-ERK1/2 expression. • iTBS promotes microglia phenotypic transformation by inhibiting the MAPK pathway, which attenuates the inflammatory response. Intermittent theta burst stimulation (iTBS) has been demonstrated to be a efficacious intervention for mitigating neurological deficits following a stroke. Nevertheless, there remains a paucity of animal studies that investigate the neurobiological mechanisms contributing to its therapeutic effects. Accordingly, the present experiments focused on the effects of iTBS on behavioral and neuropathology in ischemia/reperfusion (I/R)-injured rats and explored the underlying mechanisms. A rat model of I/R injury was established through middle cerebral artery occlusion (MCAO). Sprague-Dawley (SD) rats were randomly assigned to three groups: a sham group, an MCAO group, and an iTBS + MCAO group (administered once daily for ten consecutive days). There were 18 rats in each group, and cognitive function, myelin regeneration, microglia, inflammation, and MAPK signaling pathway expression were evaluated in each group. The findings revealed that iTBS enhanced the performance of animals in Y-maze and Open Field Test and facilitated the recuperation of cognitive functions following I/R injury. Furthermore, iTBS mitigated myelin damage, facilitated myelin regeneration, simultaneously induced the conversion of microglia to a neuroprotective M2 phenotype and significantly reduced the intensity of pro-inflammatory factor storm. Subsequent studies demonstrated that iTBS enhanced cognitive function in rats subjected to I/R injury, which was partially attributed to the suppression of the ERK1/2 and JNK signaling cascades. This inhibition promoted the transformation of M2 microglia, suppressed inflammation, and created a conducive microenvironment for myelin regeneration. Potential mechanisms of iTBS to improve cognitive function in stroke rats.iTBS promotes microglia MI-type to M2-type polarization, attenuates inflammatory response, and promotes myelin regeneration through inhibition of JNK and ERK signaling pathways, thereby improving cognitive dysfunction after stroke.