Ischemic stroke pathophysiology

Abstract

Most neurons suffer irreversible damage after only a few minutes of complete cessation of blood flow. Such a condition might exist dur ing cardiac arrest. In most instances of acute focal brain ischemia, however, a state of zero blood flow exists only in the core of the ischemic region. The larger surrounding penumbral area receives reduced blood flow, which causes loss of normal function that may lead to permanent cellular damage if severe enough or uncorrected but allows for recovery if blood flow is restored. Because ischemia is clearly a process and not an instantaneous event, the potential exists for modifying the process after the clinical ictus and altering the final outcome. Experimental models suggest that successful treatment intervention must be insti tuted within a few minutes after the onset of ischemia. Previous clinical trials have failed, in part, because treatment was delayed and therefore unlikely to render a benefit. The degree of failure or success of treatment may be a continuous rather than an all or none phenomenon. Numerous animal models have been developed that allow reperfusion after variable durat ions of middle cerebral artery occlusion. Most studies have consistently shown that reperfusion within 3 hours of arterial occlusion will limit, to some degree, the size of the resulting infarction and improve other measures of outcome as well, but that reperfusion after 3 hours will have little or no benefit and could worsen the situation. In humans, the time limit for successful treatment may not be sharply del ineated as there may be a continuum of pathological change across this 3-hour period that differs in rates of progression and reversibility according to individual variables. Unders tanding the pathophysiology of reperfu-