Cytokines and Reperfusion in Ischemic Stroke

The clinical syndrome known as ischemic stroke, secondary to the occlusion of an intracranial artery, once considered an ineluctably catastrophic event, may be susceptible of being improved through the application of newly developed therapeutic interventions. The evidence favoring this optimistic outlook is based on three separate but probably interrelated observations: (1) There exists a lapse of hours, perhaps days, between the ictus (i.e., the appearance of a focal neurologic deficit or stroke) and the time when irreversible tissue injury (i.e., widespread pannecrosis) becomes demonstrable. This time interval, generally known as the therapeutic window, may be measured in hours or days depending on the degree or severity of the post occlusive ischemia. (2) Reopening the artery, within a reasonable period of time, has beneficial effects in terms of: (a) improving the neurologic function, and (b) decreasing the numbers of necrotic neurons as well as preventing the appearance of pannecrosis or infarction. (3) The progression from the early ischemic changes (potentially reversible) to the development of an infarct may be influenced by the effects of selected cytokines, in particular those of interleukin 1 (IL-1). In this review we illustrate selected structural features of the various brain lesions induced by either permanent or transient arterial occlusions. Moreover, we discuss the possible Involvement of interleukins in the progression of the brain lesion based on experiments utilizing the administration of a human recombinant IL-1 receptor antagonist. Combined with the efforts aimed at restoring the normal circulatory conditions, therapeutic interventions that inhibit specific cytokines may contribute to improve the outcome of ischemic strokes.