Acute ischemic stroke remains without an effective therapy to improve outcome. As knowledge about the basic pathophysiology has expanded, rational approaches to therapy have evolved. The frequent presence of arterial occlusion suggested that thrombolytic therapy might be a viable approach. Both clot-specific and nonspecific thrombolytic agents are currently being evaluated in clinical trials. Focal brain ischemia induces a variety of cellular consequences. Neuroprotective therapies designed to ameliorate these metabolic abnormalities are also being evaluated in clinical trials. A key feature of all these clinical trials is the rapid initiation of therapy. In the future, we can anticipate combined therapy trials with both neuroprotective and thrombolytic drugs, an approach which is likely to be more beneficial than either one in isolation.

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