Rosiglitazone Attenuates Early Brain Injury After Experimental Subarachnoid Hemorrhage In Rats

Background:Subarachnoid hemorrhage (SAH) primarily emerges subsequent to the rupture of an intracranial aneurysm. It is a fatal disease with high mortality and morbidity worldwide. SAH may also lead to hydrocephalus, cerebral vasospasm and re-bleeding associated with unfavorable outcomes. Early brain injury (EBI) appears to play a significant role in neurological damage and may be responsible for morbidity and mortality within 24-72 h after SAH. It is thought that EBI might be a trigger following cerebral vasospasm and delayed ischemic neurological deficits (DIND) in the progress of SAH. Blood brain barrier (BBB) dysfunction, inflammation, apoptosis, edema, and oxidative cascades that lead to neuronal cell death are potential mechanisms. A recent study reported that PPARy suppressed SAH-induced inflammatory responses in the basilar arteries via the inhibition of TLR4 expression and attenuated cerebral vasospasm following SAH. However, little attention has focused on the relationship between PPARy and EBI after SAH.Objective:Early brain injury (EBI) plays a crucial role in the pathological progress of subarachnoid hemorrhage (SAH). This study was designed to determine whether rosiglitazone protects the brain against EBI in rats, and discuss the role of the anti-apoptotic mechanism mediated by Bcl-2 family proteins in this neuroprotection.Methods:86 male Sprague-Dawley rats were divided into the sham group, the SAH+vehicle group and the SAH+rosiglitazone group. SAH was induced via an endovascular perforation technique and rosiglitazone (3 mg/kg) or vehicle was administered. Mortality, neurological scores, brain water content, Evans blue dye assay, TUNEL stain assay and western blot analysis were performed.Results:Rosiglitazone significantly improved mortality, neurological scores, brain water content, blood brain barrier (BBB) and apoptosis compared with the vehicle group within 24h after SAH. The TUNEL staining assay demonstrated that apoptosis was ameliorated. Caspase-3 and MMP-9 expression was reduced, whereas Bcl-2 and p-Bad was markedly preserved by rosiglitazone. A significant elevation of p-Akt was detected after rosiglitazone treatment.Conclusion:Our study demonstrated that rosiglitazone plays a neuroprotective role in EBI after SAH via attenuation of BBB disruption, brain edema and apoptosis.