Monoclonal antibody against E selectin attenuates subarachnoid hemorrhage–induced cerebral vasospasm

Abstract

Background Increasing evidence indicates that inflammatory responses are implicated in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). However, the role of adhesion molecules in SAH-induced vasospasm is less clear. This study was designed to examine the effect of a highly specific antibody, monoclonal anti–E-selectin antibody, on cerebral vasospasm in a new murine SAH model. Methods Experimental SAH was induced in C57Black/6J mice by injecting autogenous blood into the cisterna magna, and anti–E-selectin antibody was administered intravenously immediately after SAH. All animals were killed by perfusion-fixation 24 hours after SAH. The diameters of anterior cerebral arteries (ACAs) were measured after arteries were cast with gelatin and india ink. Peripheral white blood cell count was also investigated. Results The average diameters of ACA were reduced by 22% and 25% in the SAH only and SAH plus vehicle groups, respectively, when compared with the healthy control group. After treatment with 12.5, 4, and 1 μg of anti–E-selectin antibody in mice subject to SAH, the average diameter of ACA was decreased by 9%, 10%, and 22%, respectively, when compared with the healthy control group. The protective effects of anti–E-selectin antibody achieved statistical significance at doses of 12.5 and 4 μg. Animals in the SAH only and SAH plus vehicle groups exhibited leukopenia. Administration of 12.5, 4, and 1 μg of anti–E-selectin antibody reduced leukopenia, and the total white blood cell count obtained in animals treated with 12.5- and 4- μg doses were significantly higher as compared with SAH animals. Conclusions These findings provide the first evidence that anti–E-selectin antibody was effective in prevention of SAH-induced vasospasm and imply a possible role of E selectin in the pathogenesis of vasospasm after SAH.