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.
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