MicroRNA-423-5p Inhibition is Associated with Reduced Infarct Severity After Permanent Cerebral Ischemia in Rats.

Acute cerebral infarction causes irreversible injury in the infarct core and secondary damage in surrounding ischemic tissue, where apoptosis-related signaling may contribute to lesion progression. This study evaluated whether inhibition of microRNA-423-5p is associated with improved early outcomes in a rat model of permanent middle cerebral artery occlusion. Adult male Sprague-Dawley rats were assigned to Sham, permanent middle cerebral artery occlusion, permanent middle cerebral artery occlusion plus negative-control adenovirus, or permanent middle cerebral artery occlusion plus microRNA-423-5p-interfering adenovirus groups. A stereotactic intracerebroventricular injection was performed 72 h before occlusion. Neurological deficits were assessed 24 h after surgery using the Zea Longa score; infarct volume was quantified by 2,3,5-triphenyltetrazolium chloride staining; Bax and Bcl-2 protein expression were evaluated by Western blotting; and microRNA-423-5p expression was measured by quantitative real-time polymerase chain reaction. Bioinformatic prediction was also summarized to contextualize BAX as a potential microRNA-423-5p-associated apoptosis-related gene. microRNA-423-5p inhibition was associated with lower neurological deficit scores, reduced infarct volume, decreased Bax expression, increased Bcl-2 expression, and reduced microRNA-423-5p abundance in ischemic brain tissue. These findings support a preliminary association between inhibition of microRNA-423-5p and reduced injury severity after permanent cerebral ischemia. However, direct target validation and direct apoptosis assays are required to define the underlying mechanism.