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.

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

“…Human recombinant Cu-Zn SOD has been found to prevent VS at 2 -4 days in a rabbit SAH model and to prevent the appearance of endothelial lesions (236). In a cisternal talc injection model which induced strong VS at 3 -7 days, it was found that SOD significantly inhibited the VS and almost abolished the associated myonecrosis and cell junction detachment (237).…”

Inhibitory Effect With Antisense Mitogen-Activated Protein Kinase Oligodeoxynucleotide Against Cerebral Vasospasm in Rats

“…Considering that free radicals or cytokines are associated with the pathogenesis of cerebral vasospasm after SAH, 31,32 part of the mechanisms of vasospasm might be mediated by the activation of MAPK. Gerthoffer et al 7 and Hedges et al 8 have speculated that MAPK activation mediates cerebral vasospasm because MAPK activation induces the phosphorylation of caldesmon that, in turn, leads to vascular smooth muscle contraction.…”

Intracisternal Increase of Superoxide Anion Production in a Canine Subarachnoid Hemorrhage Model

“…5,6 In support of the theory that ROS are primary pathogens for SAH, a variety of antioxidants have been shown to attenuate cerebral vasospasm in animals and humans. [7][8][9][10][11][12][13][14] We have shown that intracisternal overproduction of ⅐O 2 Ϫ may initiate and/or mediate cerebral arterial vasoconstriction and subsequent structural damage. 3 Moreover, administration of ferrous (Fe 2ϩ ) or ferric (Fe 3ϩ ) iron chelators was shown to mitigate against cerebral vasospasm, providing evidence that the iron-catalyzed Haber-Weiss and Fenton reactions are involved in the mechanism of ROS generation leading to the occurrence of cerebral vasospasm.…”