Protective Effects of Astragaloside IV on Delayed Cerebral Vasospasm in an Experimental Rat Model of Subarachnoid Hemorrhage.

Abstract

Delayed cerebral vasospasm is an important cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH). This study aimed to assess the effects of Astragaloside IV (AS-IV) on delayed cerebral vasospasm after SAH. A rat model of SAH was established by puncturing one side of the internal carotid artery. Then, rats received daily intraperitoneal injections of AS-IV (20 mg/kg; SAH-AS-IV group), 0.1% dimethyl sulfoxide (DMSO) (SAH-DMSO group), or saline (SAH group) for 5 days; an additional control group consisted of rats receiving sham surgery and saline injections. Morphologic characteristics of the basilar artery (BA) were measured from histologic sections stained with hematoxylin and eosin and used as indicators of cerebral vasospasm. Immunohistochemistry was used to detect Toll-like receptor-4 (TLR4) and nuclear factor kappa B (NF-κB) p65 protein levels in the BA. Enzyme-linked immunosorbent assay was used to measure the plasma concentrations of tumor necrosis factor-alpha and interleukin-6. Compared with controls, the SAH-DMSO and SAH groups showed increased wall thickness and reduced luminal cross-sectional area (indicative of vasospasm) and increased TLR4 expression and enhanced NF-κB activation in the BA, as well as elevated plasma levels of tumor necrosis factor-alpha and interleukin-6. Administration of AS-IV was associated with significant attenuation of all the aforementioned changes induced by SAH (P < 0.05). AS-IV may attenuate delayed cerebral vasospasm after SAH through inhibition of TLR4/NF-κB-mediated inflammatory signaling pathways.