The Role Of HIF-la In Early Brain Injury After Experimental Subarachnoid Hemorrhage In Rats

PurposeAlthough hypoxia-inducible factor-la (HIF-1α) has been extensively studied in brain injury following hypoxia-ischemia, the role of HIF-la in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. The present study was under taken to investigate a potential role of HIF-la and its related mechanism in EBI after SAH.MethodsSixty Sprague-Dawley rats were randomly divided into sham+vehicle, SAH+2-methoxyestradiol (2ME2), and SAH+vehicle groups. The SAH model was induced by endovascular perforation. After24h of SAH, the amount of blood-brain barrier (BBB) disruption, brain water content, cell apoptosis, and expression of cerebral HIF-la, BNIP3and VEGF in all groups were assayed. Double immunolabeling was used to identify cell types in which HIF-la was expressed and whether some nuclei were stained positively for both HIF-la and TUNEL. Mortality and neurological scores were recorded after24h of SAH. ResultsCompared with the sham+vehicle group, the SAH+vehicle group animals have significantly upregulated expressions of HIF-la, BNIP3, and VEGF, in addition to the increased cell apoptosis, BBB permeability, brain edema and neurological function deficit. Treatment with2ME2suppressed the expression of HIF-la, BNIP3and VEGF and reduced cell apoptosis, BBB permeability, brain edema, and neurologic scores. Double fluorescence labeling revealed that HIF-la was expressed predominantly in the nuclei of neurons and TUNEL-positive cells.ConclusionOur work demonstrated that HIF-la may play a role in EBI, causing cell apoptosis, BBB disruption, and brain edema by up-regulating its downstream targets, BNIP3and VEGF. These effects were blocked by the HIF-la inhibitor,2ME2.