Bax inhibitor-1 is required for resisting the Early Brain Injury induced by subarachnoid hemorrhage through regulating IRE1-JNK pathway

Background and Purpose: Bax inhibitor-1 (BI-1) has been identified as a suppressor of Bax-mediated cell apoptosis by regulation of endoplasmic reticulum stress-induced cell death. However, the role of BI-1 in Early Brain Injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. In the present study, we aim to explore the neuroprotective functions of BI-1 in EBI after SAH by using models of SAH that induced endovascular perforation in rats. Method: The neurological score, brain water content and blood-brain barrier (BBB) permeability were evaluated simultaneously as prognostic indicators. Western blot, RT-PCR and TUNEL staining were performed to study the role and mechanisms of BI-1 in EBI after SAH. Results: We found that BI-1 knockdown increased histological injury and the percentages of TUNEL-positive neuron in hippocampal, promoted the expressions of endoplasmic reticulum (ER) stress proteins inositol-requiring enzyme 1 alpha (IRE1 alpha) and TNF receptor-associated factor 2 (TRAF2), and increased the activation levels of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) in the hippocampus of SAH rats compared with rats in SAH + vehicle group. Conclusion: Our results indicate that BI-1 may participate in the regulation of EBI after SAH by regulating IRE1-JNK pathway. Thus, the results suggest that BI-1 may be a potential therapeutic target for SAH treatment.