The increase of serum miR-124 contributes to intestinal barrier injury in acute ischemic stroke

Abstract Intestinal barrier dysfunction is common in acute ischemic stroke (AIS) and plays a vital role in prognosis of AIS. Aberrant expression of miRNAs was a critical element not only in the pathogenesis of AIS, but also in intestinal barrier function. The present study aims to reveal the connection between the altered miR-124 and intestinal barrier dysfunction in AIS, and further elucidate the detailed molecular mechanism. In the present study, the serum miR-124 and the serum markers of intestinal barrier injury, d-Lactate and double amine oxidase (DAO), were detected to conduct correlation analysis in clinically. Then, medial cerebral artery occlusion (MCAO) mice were constructed to verify the correlation. The results showed that the elevated miR-124 in serum had a positive correlation with the exacerbated intestine barrier injury not only in clinical, but also in MCAO mice. Moreover, antagomir-124, miR-124 inhibitor, was used in MCAO mice and could relieve the intestinal barrier injury induced by AIS. Finally, miRanda software analysis, luciferase reporter assay, real-time PCR, immunohistochemistry, TUNEL assay, and western blotting were used to elucidate its mechanism. The findings revealed that miR-124 could reduce the expression of Claudin8 (CLDN8) and Occludin (OCLN) via directly targeting their 3’UTR, and antagomir-124 reversed the reduction of CLDN8 and OCLN in MCAO mice. In conclusion, the increased miR-124 in AIS could contribute to intestinal barrier injury via down-regulating the expression of CLDN8 and OCLN. Moreover, the blockade of miR-124 could alleviate intestinal barrier injury in AIS. MiR-124 may be a promising therapeutic target for prevention of post-stroke infection.