Simvastatin improves cerebrovascular injury caused by ischemia-reperfusion through NF-?B-mediated apoptosis via MyD88/TRIF signaling

Abstract

Cerebrovascular injury is the most prevalent human cerebrovascular disease and frequently results in ischemic stroke. Simvastatin may be a potential therapeutic agent for the treatment of patients with cerebrovascular injury. The present study aimed to investigate the efficacy of and the potential mechanisms regulated by simvastatin in a rat model of ischemia-reperfusion (I/R)-induced cerebrovascular injury. Cerebrovascular injury model rats were established and were subsequently treated with simvastatin or a vehicle control following I/R injury. Cell damage, neurological functions and neuronal apoptosis were examined, as well as the nuclear factor (NF)-?B-mediated myeloid differentiation primary response protein 88 (MyD88)/toll-interleukin-1 receptor domain-containing adapter molecule 1 (TRIF) signaling pathway following simvastatin treatment. The results of the present study demonstrated that simvastatin treatment led to a reduction in cell damage, improvement of neurological functions and decreased neuronal apoptosis compared with vehicle-treated I/R model rats, 14 days post-treatment. In addition, simvastatin treatment reduced cerebral water content and blood-brain barrier disruption in cerebrovascular injury induced by I/R. The results also revealed that simvastatin treatment inhibited neuronal apoptosis via the NF-?B-mediated MyD88/TRIF signaling pathway. In conclusion, simvastatin treatment may reduce I/R-induced neuronal apoptosis via inhibition of the NF-?B-mediated MyD88/TRIF signaling pathway.