Early exercise intervention alleviates neuroinflammation after ischemic stroke by regulating GSK-3β/HK2-associated inflammatory signaling in microglia.

Microglia-mediated inflammation plays a critical role in secondary brain injury following ischemic stroke. Glycogen synthase kinase-3β (GSK-3β) and hexokinase 2 (HK2) are involved in regulating microglial inflammatory responses and can promote the release of pro-inflammatory factors under ischemic and hypoxic conditions, thereby exacerbating brain damage. Early exercise intervention has been shown to improve post-stroke neuroinflammation, but whether it exerts this effect by modulating GSK-3β/HK2-associated inflammatory signaling in microglia remains unclear. This study aimed to investigate the effects of early exercise on microglial inflammation and the potential involvement of GSK-3β/HK2 signaling. A twenty-eight-day early exercise regimen was applied in a rat model of middle cerebral artery occlusion (MCAO), and complementary in vitro experiments were conducted using BV2 microglial cells under oxygen-glucose deprivation. Results demonstrated that early exercise significantly improved neurological outcomes and reduced brain tissue damage, accompanied by decreased expression of microglial pro-inflammatory factors (IL-6, TNF-α, CD86, and iNOS) and increased levels of anti-inflammatory factors (IL-10 and Arg1). In vitro, inhibition of GSK-3β in BV2 cells markedly alleviated inflammatory responses under hypoxic conditions. In conclusion, early exercise intervention can attenuate post-stroke neuroinflammation, potentially by modulating GSK-3β/HK2 signaling in microglia to regulate.