Xuesaitong injection paired with enriched environment displays neuroprotective effects and promotes functional rehabilitation by activating the PI3K/AKT/mTOR pathway

Background : Xuesaitong injection (XST), a well-known traditional Chinese patent medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. Enriched environment (EE) has been shown to play pivotal roles in functional rehabilitation following brain injury. However, the effects and exact underlying mechanisms of combination administration of XST with EE before and after ischemic stroke remain to be thoroughly elucidated. Purpose : This study aims to investigate the effects and the potential mechanisms of XST injection combined with EE on ischemic stroke. Methods : In the current study, a tMCAO (transient middle cerebral artery occlusion) mouse model was established, and then the experimental animals were intervened with XST injection combined with EE for consecutive 7 days before and after MCAO surgery respectively. Subsequently, the effects and the potential molecular mechanisms on the functional rehabilitation of the mice with stroke were further explored. Results : Animal experiments demonstrated that administration of XST combined with EE before and after the onset of acute ischemic stroke could exert protective effects against stroke initial injure and improve overall function rehabilitation. Furthermore, the inhibition of PI3K/AKT pathway by LY294002 abolished these curative effects of the intervention on brain injury, neuroinflammation, and neuron apoptosis following ischemic stroke. Conclusion : The current study provides a novel therapeutic strategy by which XST combined with EE alleviates brain injury and promotes the outcome of ischemic stroke. The PI3K/AKT/mTOR signaling pathway was highly considered as a vital role in the neuroprotective effects of XST paired with EE on ischemic brain injury.