Berberine Attenuates Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage Via Modulating AMPK/Rho Pathway

Abstract

Purpose: Our goal is to clarify the effectiveness of berberine BBR on cerebral vasospasm induced by subarachnoid hemorrhage. Methods: Thirty male Sprague-Dawley rats 350–400 g were randomly allocated to five groups sham group, SAH, BBR, SAH+BBR1 or SAH+BBR2. Experimental SAH model was induced by applying autologous blood into the cisterna magna at interval of 48 hours. To evaluate early and late effects of BBR, we allocated BBR treated groups as SAH+BBR1 and SAH+BBR2 respectively, received BBR at a dose of 20 mg/kg 15 minutes and 6 hours after first SAH induction . Rats were sacrificed on 72-hour after the study onset. Cross-sections of basilar artery was investigated by histologically. Total antioxidant status TAS and total oxidant status TOS of brain tissue were studied by spectrophotometric assay. Oxidative stress index OSI was calculated. NAPPH Oxidase 4 NOX4 enzyme levels were measured by ELISA method. Endothelial nitric oxide synthase e-NOS , phosphorylated e-NOS pe-NOS , AMP-activated protein kinase AMPK , phosphorylated AMPK pAMPK , Rho kinase and cingulin protein expressions were detected by Western blot analysis. Results: SAH+BBR1 and SAH+BBR2 groups significantly demonstrated lower OSI values, increased basilar artery cross-sectional luminal area in comparison with the SAH group. Increased Phosho-eNOS, eNOS, P-AMPK levels and Cingulin expression, decreased Nox4 and Rho-kinase levels were shown in BRB treated SAH groups relative to the SAH group. Conclusion: Berberine might be a neuroprotective agent to improve impaired cerebrovascular spasm.

Keywords

• berberine, subarachnoid hemorrhage, cerebral vasospasm, AMP-Activated Protein Kinase, Rho kinase, endothelial dysfunction

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