Prophylactic neuroprotection for cerebral ischemia.

Abstract

Treatments for acute ischemic stroke have evolved as knowledge about the pathophysiology of ischemic brain injury has advanced. Treatment strategies under development are aimed at offering neuroprotection acutely after focal cerebral ischemic injury, but delayed initiation of therapy may reduce efficacy. Pretreatment before ischemia begins could offer distinct advantages in patient groups at high risk for ischemic stroke. If a neuroprotective drug were available orally, safe, and relatively inexpensive, it could be considered for prophylactic use in high-risk populations. Prophylactic neuroprotection would include (1) short-term neuroprotection before and after high-stroke risk procedures, (2) long-term neuroprotection for primary and secondary intervention in populations at high risk for stroke, and (3) concomitant neuroprotection with agents that have multiple treatment effects. Patients undergoing procedures such as cardiac surgery, endarterectomy, or endovascular therapy, which have a risk of cerebral ischemic events during a defined period, might be considered for short-term, periprocedure prophylactic neuroprotection. Several populations at high long-term risk for initial ischemic stroke have been identified and include those with combinations of vascular risk factors, transient ischemic attacks, atrial fibrillation, and asymptomatic carotid stenosis. Such people, as well as those at risk for stroke recurrence after minor strokes, are readily identifiable and perhaps appropriate for long-term prophylactic neuroprotection. Patients with hypertension and cerebrovascular atherosclerosis have a high stroke risk, and therapies directed at these underlying disorders are available that also have concomitant neuroprotective effects. An ideal drug for trials in these patient groups has not yet been developed, and establishing its efficacy may prove to be an arduous and lengthy task. The possibility of ameliorating the consequences of an acute ischemic stroke by pretreating high-risk patients with appropriate neuroprotective agents needs to be explored. Several types of high-risk population for prophylactic neuroprotection can be envisioned and then studied in clinical trials.