Overexpression of microRNA-21 protects spinal cords against transient ischemia.

OBJECTIVE: MicroRNA (miRNA) molecules are involved in the response of the central nervous system to ischemia and reperfusion. We sought to test the hypothesis that overexpression of miRNA-21 can induce neuroprotection on spinal cords against transient ischemia.

METHODS: Overexpression of miRNA-21 in vivo was conducted by means of intrathecal injection of lentivirus vectors containing pre-miRNA-21. The vehicle or control lentivirus vectors were given to the control group and the control vector group, respectively. Five days later, spinal cord ischemia was accomplished in rats by crossclamping the descending aorta just distal to the left subclavian artery for 14 minutes. Hind-limb motor function was assessed during 48 hours after ischemia using the Motor Deficit Index, and histologic examination was performed. Expressions of caspase-3, Fas ligand (Faslg), programmed cell death 4 (PDCD4), and miRNA-21 in the spinal cord were evaluated by quantitative real-time polymerase chain reaction and western blot analysis.

RESULTS: Transfection of pre-miRNA-21 significantly enhanced expression of miRNA-21 in the spinal cord (P < .01 vs the control group) and dramatically downregulated expressions of caspase-3, Faslg, and PDCD4 (P < .01 vs the control group). Compared with the control group, Motor Deficit Index scores at 6, 12, 24, and 48 hours after reperfusion were markedly lower in rats with overexpression of miRNA-21 (P < .01). Histologic examination showed that many more intact motor neurons were preserved in the lumbar spinal cord of rats with overexpression of miRNA-21 (P < .01 vs the control group).

CONCLUSIONS: Overexpression of miRNA-21 exerts neuroprotective effects on spinal cords against ischemia-reperfusion injury, possibly by inhibition of the proapoptotic proteins Faslg and PDCD4.