Upregulation of MiRNA-149-5p Reduces the Infract Volume in Middle Cerebral Artery Occlusion Rats by Modulating Cation-Chloride Cotransporters Expressions

Abstract

Background: Brain ischemia often leads to the chloride gradient alternations, which affects volume regulation and neuronal survival. Increase in NKCC1 expression and reduction in KCC2 level under ischemic condition results in inflammation and neuronal death. In this study, we investigated the effect of mimic miRNA and coenzyme Q10 (CoQ10) on the expression of cation-chloride cotransporters (CCCs) (NKCC1 and KCC2) after cerebral ischemia.

Methods: In this study, cerebral ischemia was modeled using the middle cerebral artery occlusion method. Rats were randomly divided into six groups: sham, model, negative control, vehicle, and the first and second treatments. In the Sham group, ischemia was not induced, and no treatment was performed. In the Model group, ischemia induction was performed, and other groups, in addition to ischemia induction, received Scramble miRNA, Ethanol, mimic miRNA-149-5p and CoQ10, respectively. Each group was divided into three subgroups to assess the volume of the tissue damage and neurological deficits scores (NDS) in subgroup 1, brain water content in subgroup 2, level of miRNA-149-5p and CCC expressions in subgroup 3.

Results: Our data suggested that the use of mimic miRNA and Q10 increased the level of miRNA-149 and KCC2 expression and decreased NDS, NKCC1 expression, brain water content, and infract volume.

Conclusion: Findings of this study suggest that the mimic miRNA and Q10 may have neuroprotective effects through reducing infract volume and brain water content and modulating the expression of CCCs after brain ischemia.