MiR-191 downregulation protects against isoflurane-induced neurotoxicity through targeting BDNF

Isoflurane inhalation can cause nerve damage, and miR-191 is abnormally expressed in nerve crush injuries. This study aimed to explore the effect of miR-191 on isoflurane-induced cognition impairment and neurotoxicity in vivo and in vitro, as well as its potential mechanism.

Sprague-Dawley male rats and primary hippocampal neurons were applied and exposed to 2% isoflurane. The level of miR-191 was regulated both in vitro and in vivo to investigate the role of miR-191 in isoflurane-induced neurotoxicity. Morris water maze assay was used to evaluate the neurological function of rats. The level of miR-191 was measured by qRT-PCR. CCK-8 assay and Flow cytometry were applied to detect the cell viability and apoptosis. Dual luciferase reporter gene detection was used for the target gene analysis.

miR-191 was up-regulated in the hippocampal tissues of rats exposed to isoflurane. Downregulation of miR-191 ameliorated isoflurane-induced cognition impairment, including the increase of the neurological score and the escape latency, and the decrease of the time spent in the original quadrant for the rats exposed to isoflurane. Isoflurane exposure inhibited hippocampal neuron viability and promoted cell apoptosis, which was reversed by down-regulation of miR-191. BDNF is a target gene of miR-191.

Isoflurane causes some neurotoxic effect which is mediated through miR-191 abnormal expression targeting BDNF. Downregulation of miR-191 has a protective role against isoflurane-induced neurotoxicity, regulates the vitality and slows down neuronal cell apoptosis.