Pathogenesis of vasogenic edema in focal cerebral ischemia. Role of superoxide radicals.

Oxygen-derived free radicals have been postulated to be involved in brain edema and cell death secondary to ischemia and traumatic injury. Using a model of vasogenic brain edema produced by a permanent occlusion of the left MCA in rats, we have studied the role of superoxide radicals in pathogenesis of ischemic edema. The levels of NBF in ischemic brain were increased by 222%, 420%, and 614%, respectively, at 1, 4, and 24 hr after the MCAO. Topical application of superoxide dismutase to the injured cortex through a modified cranial window significantly reduced the NBF levels, indicating the involvement of superoxide radicals in ischemic brain. Liposome-entrapped SOD, when IV injected 5 min after the MCAO, significantly reduced the degree of edema at 24 hr. Our data indicate that superoxide radicals play an important role in the pathogenesis of vasogenic edema in cerebral ischemia.