LGALS9 Is Beneficial to the Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation on Ischemic Stroke

We aimed to investigate whether LGALS9 contributes to the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of ischemic stroke (IS) in rats.

The model of cerebral ischemia in rats was established via middle cerebral artery occlusion (MCAO). After being injected with LGALS9 siRNA prior to MCAO surgery and undergoing rTMS intervention postoperatively, the rats were evaluated for neurological function using the modified neurological severity score (mNSS) and for behavioral function through the foot-fault test and Rotarod test. Brain tissues were collected, and pathological changes were observed. Levels of IL-1β, IL-6, and IL-18 were assessed using ELISA. Immunohistochemistry was employed to detect CD86 expression, while RT-qPCR and Western blot were used to detect LGALS9 expression.

MCAO rats showed higher mNSS scores, more foot-fault errors, shorter Rotarod duration, elevated IL-6, IL-18, and IL-1β levels, decreased LGALS9 expression, increased CD86 expression, severe brain damage with increased apoptotic neurons, and elevated neuropathological injury scores. rTMS intervention improved the neurological function of MCAO rats and alleviated the inflammatory response in brain tissues, and LGALS9 enhanced the improvement effects induced by the rTMS intervention.

rTMS can improve neurological function, reduce inflammatory responses, and protect brain tissue in rats with IS, effects for which LGALS9 is required to achieve the full benefit. The molecular mechanisms of the rTMS‑LGALS9 pathway remain unclear, as its downstream signaling and effects on neurological function and inflammation are not fully elucidated. Moreover, findings from animal models require further validation for human disease relevance and clinical translation.