Blood flow independent effects of rt-PA in a model of permanent cerebral ischemia: deterioration of ischemia induced cell death

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…