cerebral ischemia-reperfusion induced neuronal damage, inflammation, mir-374a-5p, mapk6, nlrp3, and smad6 alterations: rescue effect of n-acetylcysteine

Background: ischemic stroke (is) is still a major cause of neurological disability. this study aimed to ascertain potential markers closely related to is diagnosis and treatment and then we examined the neuroprotective effect of n-acetylcysteine (nac) in a transient cerebral ischemia. methods: male wistar rats were randomly divided into three groups (n=6), including sham, ir (ischemia-reperfusion), ir+nac (150 mg/kg, ip; intraperitoneally, 1 hour prior to ischemia and 5 min before reperfusion). the infarct volume was evaluated by 2,3,5-triphenyl tetrazolium chloride staining. h&e and nissle staining were performed to evaluate cerebral ischemia-reperfusion injury. mir-374a-5p gene expression, mapk6, nlrp3, smad6, tnf-α, and il-1β protein levels were determined by real-time pcr, western blot, and elisa in the cerebral cortex exposed to ir. results: herein, we found that ir increased infarct volume and pathological damage to the cerebral cortex after global cerebral artery occlusion/reperfusion. in addition, mir-374a-5p gene expression decreased, while mapk6, nlrp3, and smad6 protein expressions increased in the ir group. tnf-α and il-1β protein levels increased in the ischemic cortex. treatment with nac significantly attenuated infarct size, inflammation and reversed aforementioned molecule levels. conclusion: taken together, these results suggested that ischemic insult can increase infarct size, neuronal damage, and inflammation may in part by modulating mir-374a-5p, mapk6, nlrp3, and smad6 pathway in the brain cortex after cerebral ir insult and providing new clues to molecular mechanisms and treatment targets in is. it can be alleviated by nac as a potential therapy for someone afflicted with ischemia.