Effects of ebselen versus nimodipine on cerebral vasospasm subsequent to experimental subarachnoid hemorrhage in rats

Abstract

We investigated the effect of ebselen relative to nimodipine in an animal model of subarachnoid hemorrhage. Thirty Wistar albino rats were divided into 5 groups: G1, no intervention; G2, sham surgery without subarachnoid hemorrhage (SAH); G3, SAH only; G4, SAH plus nimodipine treatment; G5, SAH plus ebselen treatment. For G2 animals, physiological saline (0.9% NaCl) was injected into the cisterna magna. For G3, G4 and G5 animals, SAH was induced by injecting autologous non-heparinized blood into the cisterna magna. One hour after injection, G4 animals received nimodipine at 6-hour intervals and G5 animals received ebselen twice a day for 48 hours. After treatment, brain tissue and blood samples were taken for biochemical and histopathological examination. Mean malonyldialdehyde concentration was significantly higher in G3 than in G1 ( p < 0.0001), G2 ( p = 0.01), G4 ( p = 0.002) and G5 ( p = 0.014), and significantly higher in G5 than in G1 ( p = 0.013). Mean superoxide dismutase activity was significantly lower in G4 than in both G1 ( p = 0.025) and G2 ( p = 0.02). Mean wall thickness was significantly greater in G3 than in G1 ( p < 0.0001), G2 ( p = 0.01), G4 ( p < 0.0001) and G5 ( p < 0.0001). Mean wall thickness was also significantly greater in both G1 and G2 than in G4 ( p < 0.0014 and p < 0.0001) and G5 ( p < 0.0001 and p < 0.0001). Mean luminal diameter of the basilar artery was significantly smaller in G3 than in G2 ( p = 0.02), G4 ( p < 0.018) and G5 ( p < 0.001). Our results confirm that ebselen may have neuroprotective effects by acting to prevent vasospasm.