Abstract
Background: Ischemic stroke is a leading global cause of death, and its severity is increased by inflammatory pathways. N-acetylcysteine (NAC), an FDA-approved anti-inflammatory agent, can significantly affect pro-inflammatory cytokines. On the other hand, microRNAs such as microRNA-342-3p (miR-342-3p), which likely play a role in reducing inflammation, could be a promising factor in the investigation of ischemic stroke. This research aims to investigate the impact of NAC on miR-342-3p expression and its downstream gene Chi3l1 in animal models with middle cerebral artery occlusion (MCAO). Methods: Rats were divided into four groups: MCAO, sham, NAC-only, and NAC+MCAO. The MCAO group underwent MCAO surgery without any treatment. In the NAC-only group, 150 mg/kg NAC was injected without MCAO surgery. Rats in the NAC+MCAO group were subjected to MCAO surgery, followed by 150 mg/kg NAC administered twice a day, 1 and 6 h after surgery. In all groups, neurological deficits, infarction volume, cerebral edema, blood-brain barrier permeability, and miR-342-3p/Chi3l1 gene expression levels were evaluated. Results: This study demonstrated notable differences in behavioral tests, blood-brain barrier permeability, and cerebral edema between the MCAO and NAC+MCAO groups. Infarct volume was significantly reduced in the NAC+MCAO group compared to the MCAO group. Also, miR-342-3p gene expression was down-regulated in the MCAO group, while its expression was up-regulated in the NAC+MCAO group. Chi3l1 gene expression was reduced in the NAC+MCAO group. In addition, a significant correlation was observed between miR-342-3p and Chi3l1 expression levels. Conclusion: This study supported the neuroprotective effect of NAC on reducing stroke damage in an animal model. Also, these findings provided evidence that the role of NAC in ischemia might be related to modulating the pathway of inflammation (through alleviating the expression of miR-342-3p and Chi3l1).