MicroRNA-124 expression in the brains of rats during early cerebral ischemia and reperfusion injury is associated with cell apoptosis involving STAT3.

Abstract

Cerebral ischemia and reperfusion injury is a cause of death and disability in adults. MicroRNA-124 possesses protective effects against apoptosis in cerebral ischemia and reperfusion. To provide insights into the diagnosis and treatment of cerebral ischemia and reperfusion injury, the dynamic changes of microRNA-124 expression during the early stage of cerebral ischemia and reperfusion injury in rats was investigated by quantitative polymerase chain reaction. To elucidate the association between the dynamic expression of microRNA-124 and apoptosis, the expression of proteins associated with apoptosis, including caspase-3, apoptosis regulator Bcl-2 (Bcl-2) and apoptosis regulator Bax (Bax) was analyzed by immunohistochemistry and western blot analyses. As signal transducer and activator of transcription 3 (STAT3) is involved in cell apoptosis and associated with Bcl-2, the protein expression of STAT3 and its active form, phosphorylated (p-)STAT3, were analyzed by western blot analysis. The expression of microRNA-124 increased and the maximum value appeared 12 h after reperfusion. Similarly, the expression of Bcl-2 also peaked 12 h after reperfusion, however the expression of caspase-3 and Bax continued to increase after the 12 h time point. These results indicate that the expression of microRNA-124 is closely associated with Bcl-2 and serves a protective role, inhibiting apoptosis. As the upstream regulator of Bcl-2, the expression of p-STAT3 was in accordance with Bcl-2 expression and peaked 12 h after reperfusion. By contrast, STAT3 was downregulated and the minimum level of STAT3 protein was reached 12 h after reperfusion. In summary, during the early stage of cerebral ischemia and reperfusion, the dynamic expression of microRNA-124 exhibited protective effects through the inhibition of apoptosis via anti-apoptotic proteins Bcl-2 and STAT3. Conversely, caspase-3 and Bax maintain apoptosis. The present study provides evidence to aid in the understanding of cerebral ischemia and reperfusion injury and develops methods of diagnosis and therapy of this condition.