CYTOKINES AND REPERFUSION IN ISCHEMIC STROKE

The clinical syndrome known as ischemic stroke, secondary to the occlu sion of an intracranial artery, once considered an ineluctably catastr ophic event, may be susceptible of being improved through the applicat ion of newly developed therapeutic interventions. The evidence favorin g this optimistic outlook is based on three separate but probably inte rrelated observations: (1) There exists a lapse of hours, perhaps days , between the ictus (i.e., the appearance of a focal neurologic defici t or stroke) and the time when irreversible tissue injury (i.e., wides pread pannecrosis) becomes demonstrable. This time interval, generally known as the therapeutic window, may be measured in hours or days dep ending on the degree or severity of the post occlusive ischemia. (2) R eopening the artery, within a reasonable period of time, has beneficia l effects in terms of: (a) improving the neurologic function, and (b) decreasing the numbers of necrotic neurons as well as preventing the a ppearance of pannecrosis or infarction. (3) The progression from the e arly ischemic changes (potentially reversible) to the development of a n infarct may be influenced by the effects of selected cytokines, in p articular those of interleukin 1 (IL-1). In this review we illustrate selected structural features of the various brain lesions induced by e ither permanent or transient arterial occlusions. Moreover, we discuss the possible involvement of interleukins in the progression of the br ain lesion based on experiments utilizing the administration of a huma n recombinant IL-1 receptor antagonist. Combined with the efforts aime d at restoring the normal circulatory conditions, therapeutic interven tions that inhibit specific cytokines may contribute to improve the ou tcome of ischemic strokes.