366 Effects of Osthole on Early Brain Injury and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model

INTRODUCTION: Early brain injury (EBI) and cerebral vasospasm are major complications of aneurysmal subarachnoid hemorrhage (aSAH) that significantly increase mortality and morbidity. Prevention of these complications is crucial; however, despite extensive research, current treatments remain inadequate. METHODS: 40 Wistar Albino rats were randomly divided into four groups: Sham (n = 10), SAH (n = 10), Osthole (n = 10), SAH + Osthole (n = 10). SAH was induced in groups 2 and 4 by injecting autologous blood into the cisterna magna. Groups 3 and 4 received osthole (30 mg/kg) intraperitoneally once daily for 5 days.On the fifth day, all rats were sacrificed. Hematoxylin and eosin (H&E) staining was used to prepare transversal sections of the brainstem and basilar artery for comparison of vessel wall thickness and lumen diameter. Immunohistochemical staining was performed to assess the expression of hypoxia-inducible factor 1α (HIF-1α), Bcl-2, and caspase-3 proteins. Reactive oxygen species (ROS) levels were measured using luminol and lusiginin chemiluminescence in perivascular brain tissue samples from the basilar artery. RESULTS: H&E staining revealed that osthole treatment significantly reduced basilar artery wall thickening and lumen narrowing observed in the SAH group. Immunohistochemical staining demonstrated increased caspase-3 expression and decreased Bcl-2 expression following SAH, which were reversed by osthole. Immunohistochemical staining for HIF-1α showed a reduction in SAH-induced HIF-1α levels with osthole treatment. Chemiluminescence measurements indicated increased ROS in the SAH group compared to the control group, and osthole treatment significantly reduced this increase. With osthole treatment, an improvement was observed in the modified neurological severity score. CONCLUSIONS: Our study demonstrates osthole's anti-apoptotic, antioxidant, and vasodilatory effects in an experimental aSAH model. The results indicate that osthole has the potential to function as a therapeutic agent for EBI and cerebral vasospasm.