REPERFUSION INJURY AFTER FOCAL CEREBRAL-ISCHEMIA - THE ROLE OF INFLAMMATION AND THE THERAPEUTIC HORIZON

RECENT EVIDENCE INDICATES that thrombolysis may be an effective therap y for the treatment of acute ischemic stroke. However, the reperfusion of ischemic brain comes with a price. In clinical trials, patients tr eated with thrombolytic therapy have shown a 6% rate of intracerebral hemorrhage, which was balanced against a 30% improvement in functional outcome over controls. Destruction of the microvasculature and extens ion of the infarct area occur after cerebral reperfusion. We have revi ewed the existing data indicating that an inflammatory response occurr ing after the reestablishment of circulation has a causative role in t his reperfusion injury. The recruitment of neutrophils to the area of ischemia, the first step to inflammation, involves the coordinated app earance of multiple proteins. Intercellular adhesion molecule-1 and in tegrins are adhesion molecules that are up-regulated in endothelial ce lls and leukocytes. Tumor necrosis factor-alpha, interleukin-1, and pl atelet-activating factor also participate in leukocyte accumulation an d subsequent activation. Therapies that interfere with the functions o f these factors have shown promise in reducing reperfusion injury and infarct extension in the experimental setting. They may prove to be us eful adjuncts to thrombolytic therapy in the treatment of acute ischem ic stroke.