Abstract

Reperfusion with intravenous tissue plasminogen activator (tPA) has been the goal of therapy for acute ischemic stroke; however, tPA is contraindicated in many patients, has low recanalization rates in major occlusions, and carries a substantial risk of symptomatic intracerebral hemorrhage. In the present study, we hypothesized that partial intra-aortic occlusion of the abdominal aorta would increase salvage of ischemic penumbra and reduce infarct volume after focal embolic stroke in rats. We examined the effects of aortic occlusion on infarct volume, expression and activation of matrix metalloprotease-9, and hemorrhagic transformation with or without treatment with tPA. We then examined the effects of aortic occlusion on perfusion deficits following embolic occlusion. Results showed that partial aortic occlusion significantly reduces brain infarction volume with or without treatment with tPA after focal ischemia, but does not increase risk for hemorrhagic transformation or matrix metalloprotease-9 expression and activation. Partial intra-aortic occlusion also reduces perfusion deficits after focal cerebral ischemia as compared to control. The present study shows that partial intra-aortic occlusion significantly decreases infarction volume and perfusion deficits following ischemic injury in an embolic model of cerebral ischemia. Moreover, combination treatment with tPA and partial intra-aortic occlusion further reduces infarction volume without any increase in hemorrhagic transformation.

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