The role of superoxide anions in the pathogenesis of cerebral vasospasm.

Abstract

To determine the role of superoxide anions in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage, we studied the preventive effect of human recombinant copper-zinc superoxide dismutase (h-r SOD) in a rabbit subarachnoid hemorrhage (SAH) model. Forty-five rabbits receiving intracisternal injection of 3 mL autologous nonheparinized blood or 3 mL saline were divided into four groups as follows: (1) saline injected and no treatment (control group, n = 6); (2) blood injected and no treatment (SAH group, n = 20); (3) blood injected and treated by multiple intracisternal injections of 30,000 U of h-r SOD in 0.5 mL saline (SOD group, n = 9); and (4) blood injected and treated by multiple intracisternal injections of 0.5 mL saline (saline group, n = 10). Serial angiograms were performed after the blood injection, and the diameter of the basilar artery was measured. Three animals from the control group and five animals from the SAH and SOD groups each were killed 2 days after SAH, and their basilar arteries were processed for transmission electron microscopic observations. In the SAH and saline groups, the diameter of the basilar arteries was significantly reduced (28 +/- 14% and 27 +/- 9%, respectively) at 2 days after the blood injection, then recovered to pre-SAH levels until 11 days. In the SOD group, the diameter of the basilar artery was only minimally changed during the follow-up period. Transmission electron microscopy revealed endothelial injury in all basilar arteries in the SAH group, whereas endothelial injury was minimal in the SOD group. We determined that h-r SOD prevents the occurrence of vasospasm, possibly as a result of preventing endothelial injury initiated by superoxide anions.