Abstract
Background: Recombinant tissue plasminogen activator (rt-PA) is the only approved drug for the therapy of acute ischemic stroke. However there is raising evidence that endogenous t-PA acts as a mediator of neuronal damage in different models of neuronal cell death. Regarding its use in stroke therapy a reduced infarct volume was found in t-PA-knockout mice compared to wild type mice in transient focal cerebral ischemia. This effect was reversible by application of exogenous rt-PA. Application of rt-PA in models of transient focal ischemia in wild-type-animals led to contradicting data. Responsible were different effects on cerebral blood flow (CBF) due to reperfusion or secondary hypoperfusion, that masked possible rt-PA effects independent of its fibrinolytic properties. Therefore transient cerebral ischemia is no suitable model to investigate CBF independent effects of rt-PA on ischemia induced cell death in vivo. Consequently we chose a model of permanent focal cerebral ischemia in adult mice to exclude CBF alterations.
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