Neuroprotective effects of viral overexpression of microRNA-22 in rat and cell models of cerebral ischemia-reperfusion injury.

Several studies have reported that microRNA (MIR) is involved in the pathogenesis and progression of ischemic diseases, including cerebral ischemia, and that MIR-22 may inhibit the inflammatory response and cell apoptosis, which contribute to ischemia/reperfusion (I/R) injury. However, the specific function of MIR-22 in cerebral I/R injury remains far from clear. This study aimed to examine the potential protective effect of MIR-22 against cerebral I/R injury and its mechanism. As predicted, adenovirus-mediated MIR-22 overexpression markedly reduced the neurological score and infarct size (P < 0.05). We demonstrated that MIR-22 overexpression resulted in a reduction in inflammatory cytokines TNF-α, IL-6, COX-2, and iNOS, whereas the level of IL-10 was enhanced. MIR-22 overexpression significantly inhibited NF-κB activity by decreasing NF-κB coactivator NCOA1 expression. Furthermore, we found that MIR-22 could reduce the apoptotic rate of cortical neurons. Caspase-3 activity was inhibited by MIR-22, and the expression of the anti-apoptosis gene Bcl-2 in neurons was increased and that of the pro-apoptosis gene Bax decreased following MIR-22 overexpression. Our results suggest that MIR-22 could be used to treat cerebral I/R injury and that its neuroprotective effect may be attributed to a reduction in inflammation and apoptosis.