Significant Role of Apoptosis-Inducing Factor (AIF) for Brain Damage Following Focal Cerebral Ischemia

Abstract

Every year, stroke is responsible for the death of 5.5 million people and thus accounts for 10% of all deaths in industrialized countries worldwide (Mackay and Mensah 2004). Despite such a high incidence and mortality, therapeutic options for stroke patients are still very limited (Lo et al. 2003). Currently, the only clinical treatment option for stroke is reperfusion therapy by local or systemic administration of recombinant tissue plasminogen activator (rtPA). A major drawback of rtPA, however, is that it may be fatal if given in hemorrhagic stroke, which has clinical symptoms very similar to ischemic stroke. Accordingly, rtPA therapy can only be initiated after cerebral hemorrhage has been ruled out by brain CT or NMR imaging. By the time diagnostic procedures have been completed, the therapeutic window for rtPA, i.e. 3 h after the onset of ischemia, has commonly closed. As a result less than 5% of all stroke patients are eligible for rtPA lysis according to current protocols (Adams et al. 2007). The remaining 95% may only hope for spontaneous reperfusion, which in most cases, however, occurs too late to prevent penumbral cell death and the subsequent loss of neurological function (Molina et al. 2001). Hence, a treatment strategy is required, which prolongs neuronal survival in the ischemic penumbra, i.e. under compromised cerebral blood flow conditions, until reperfusion occurs.