Effects of recombinant human erythropoietin (rhEPO) on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage

Abstract

Previous studies have shown that recombinant human erythropoietin (rhEPO) can attenuate the degree of cerebral vasospasm following experimental subarachnoid hemorrhage (SAH). However, the mechanisms for this beneficial effect are still poorly understood. SAH-induced endothelial apoptosis may trigger, aggravate, and maintain cerebral vasospasm. We, therefore, tried to analyze whether rhEPO administration influenced the endothelial cell apoptosis in the basilar artery after SAH. Another aim of the current study was to investigate the modulation of rhEPO on the activity of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), which played an important role in the signaling of apoptosis. A total of 48 rabbits were randomly divided into four groups; control group, SAH group, SAH + vehicle group, and SAH + rhEPO group. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. The rhEPO was administered i.p. starting 5 min after the induction of SAH on day 0 and repeated every 8 h for 120 h. The basilar arteries were extracted on day 5 after SAH. As a result, we found that administration of rhEPO could activate JAK2 and STAT3 in the basilar artery and decrease the apoptosis index of endothelial cells following SAH. Moreover, the anti-apoptotic genes such as bcl-2 and bcl-xL were up-regulated after the injections of rhEPO. In conclusion, the therapeutic effect of rhEPO on the subsequent vasospasm after SAH may relate to its inhibition on the endothelial apoptosis in the cerebral arteries, which may be mediated in part by JAK2/STAT3 signaling pathway.