The potential role of JAK2/STAT3 pathway on the anti-apoptotic effect of recombinant human erythropoietin (rhEPO) after experimental traumatic brain injury of rats

Previous studies indicate that administration of recombinant human erythropoietin (rhEPO) protects cortical neurons following traumatic brain injury (TBI). The mechanisms of rhEPO's neuroprotection are complex and interacting, including anti-apoptosis. Here we aim to demonstrate the role of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway on the anti-apoptotic effect of rhEPO in Feeney free falling TBI model. Activation of JAK2/STAT3 in pericontusional cortex was analyzed among rats in Sham, TBI, TBI + rhEPO, TBI + rhEPO + AG490 groups (rhEPO: 5000 U/kg day; JAK2 inhibitor AG490: 5 mg/kg day, intraperitoneal) through Western blotting, electrophoretic mobility shift assay. Bcl-2 and Bcl-xl expression (Q-PCR, Western blotting) and cell apoptosis (TUNEL) in pericontusional cortex were also detected in each group. As a result, we found that TBI could activate JAK2 and STAT3, and increase cell apoptosis in pericontusional cortex. RhEPO enhanced the expression of p-JAK2 and p-STAT3, up-regulated the mRNA and protein levels of Bcl-2 and Bcl-xl, followed by increased cell survival. Moreover, AG490 attenuated rhEPO's neuroprotection by down-regulating rhEPO-induced activation of JAK2/STAT3, and inhibiting Bcl-2 and Bcl-xl. These results suggest the essential role of JAK2/STAT3 pathway on the anti-apoptotic benefit of post-TBI rhEPO treatment. (C) 2011 Elsevier Ltd. All rights reserved.