Amelioration of vasospasm after subarachnoid hemorrhage in transgenic miceoverexpressing CuZn-superoxide dismutase

Background and Purpose-To clarify the effect of superoxide dismutase (SOD) on vasospasm after subarachnoid hemorrhage (SAH), we investigated sequentia l changes in arterial diameter after SAH in transgenic mice overexpressing CuZn-SOD (SOD-1), Methods-SOD-transgenic mice and nontransgenic littermates (35 to 40 g) were subjected to SAH produced by endovascular perforation of left anterior cer ebral artery. At 4 hours and 1, 3, 7, and 14 days after SAH, the mice were perfused with 10% formalin and consequently with a mixture of carbon black and 10% gelatin to cast all vessels. Vasospasm was evaluated by measuring t he diameter of the left middle cerebral artery (MCA) with a microscope. Results-In nontransgenic mice, the diameter of the MCA on day 3 after SAH ( 110.5+/-20.5 mu m [mean+/-SD]; n=16) was significantly reduced compared wit h that without SAH (138.5+/-14.5 mu m; n=12) (P<0.01). Moreover, on day 3 a fter SAH, the diameter of the MCA in SOD-transgenic mice (127.9+/-20.2 mu m ; n=20) was significantly larger than that in nontransgenic mice (110.5+/-2 0.5 mu m; n=16) (P<0.05). Conclusions-These results suggest that SOD is effective on the amelioration of vasospasm after SAH and that oxygen free radicals, particularly superox ide, play an important role in the pathogenesis of vasospasm after SAH.