ABSTRACT
RATIONALE FOR NEUROPROTECTIVE STRATEGIES Embolic or in situ thrombotic occlusion of an artery supplying the brain causes focal brain ischemia, which can ultimately lead to irreversible tissue injury and infarction via a complex array of pathogenic mechanisms, termed the “ischemic cascade” ( 1 ). Thrombolytic drugs or mechanical devices can reperfuse occluded vessels, improving outcome following acute ischemic stroke (AIS). Intravenous tissue plasminogen activator (t-PA) has regulatory approval for AIS treatment within 3 h of symptom onset and, more recently, the MERCI clot retriever has been approved for removal of intracranial thrombi in AIS treatment (see Part 2, Chapter 7) ( 2 , 3 ). However, only 3% of AIS patients receive specifi c therapy ( 4 ). This percentage can be increased by extending the 3-h time window for thrombolysis and/or administering neuroprotective pharmacological agents. Neuroprotection, another therapeutic approach for acute ischemic stroke, attempts to impede the cellular mechanisms that lead to irreversible ischemic tissue injury. However, this approach has not been successful in clinical trials for several reasons ( 5 ).
