Neutralization of Interleukin-1β Reduces Vasospasm and Alters Cerebral Blood Vessel Density Following Experimental Subarachnoid Hemorrhage in Rats

Abstract

Subarachnoid hemorrhage (SAH) develops when extravasated arterial blood enters subarachnoid space and mixes with cerebrospinal fluid. As a result, many pathologies develop, including arterial vasospasm that leads to the ischemia and hypoxia. Immuno-inflammatory response is considered as the cause of numerous complications following SAH. In the study, we examined the role of one of major cytokines, interleukin 1-beta (IL-1beta), on the vascular pathologies after experimental SAH in adult rats. SAH was produced by injection of 150 uL of autologous arterial blood into cisterna magna. In 50% of animals, IL-1beta activity was inhibited by intracerebroventricular administration of anti-rat IL-1beta antibodies (SAH' groups). Control group consisted of sham-operated rats. Ninety minutes or 24 hrs following surgery, animals were perfused transcardially and whole brains were collected. Spasm index (ratio of vessel diameter to the mean wall thickness) of basilar artery as well as blood vessel density (number of vessels per square millimeter) at brain stem and frontal part of the brain were measured. SAH led to the vasospasm of basilar artery and increased the density of blood vessel. Neutralization of IL-1beta activity significantly reduced both the vasospasm and blood vessel density only 24 hrs after SAH. The results demonstrate an important role of IL-1beta in the delayed development of vascular pathologies after subarachnoid hemorrhage.