Increased Expression of Tight Junction Proteins and Blood-Brain Barrier Integrity in MCAO Rats Following Injection of miR-149-5p

Int J Mol Cell Med. 2022;11(3):223-235. doi: 10.22088/IJMCM.BUMS.11.3.223.

Abstract

Cerebral ischemia is a common neurodegenerative disease in which damage to the blood-brain barrier (BBB) is the main consequence. In cerebral ischemia, the level of miR-149-5p and tight junction proteins are decreased, while the level of Calpine is increased, finally leading to increased BBB permeability. This study investigated the effect of miR-149-5p mimic on the expression of Calpain, Occludin, and ZO-1 and the consequences of cerebral ischemia. Cerebral ischemia model was performed via middle cerebral artery occlusion (MCAO) method on female Wistar rats. Four groups of Wistar rats were studied: Sham, cerebral ischemia without treatment, Scramble miR, and miR-149-5p mimic treatment. Then, neurological defects and BBB permeability (via Evans blue staining), cerebral edema (cerebrospinal fluid percentage), and ZO-1, Occludin, and Calapin expression (by quantitative real time- PCR) were investigated. qRT-PCR results showed miR-149-5p expression decreases after cerebral ischemia induction. In addition, Occludin and ZO-1 expression significantly increased in miR-149-5p group. In contrast, Calapin expression, BBB permeability, brain water content and neurological defects were significantly decreased. It seems that the increased level of miR-149-5p exerts its protective effect on cerebral ischemia due to increasing of tight junction proteins.

Keywords: Cerebral ischemia; miR-149-5p; middle cerebral artery occlusion; tight junction.