Abstract

Background: Global cerebral ischemia initiates a cascade of pathophysiological changes that progressively impair subsequent perfusion of brain tissue. Some authors have proposed that adequate cerebral perfusion becomes impossible after approximately 10-30 minutes of global ischemia. However, the extant evidence base for this threshold and its variation across studies have not yet been systematically examined. Objective: To synthesize the literature on post-ischemic cerebral perfusion success as a function of ischemia duration. Methods: We searched PubMed (February 11, 2026) for studies of global cerebral ischemia in animal or human models that reported quantitative or categorical measures of perfusion quality. Eligible studies included those assessing perfusion via restoration of blood flow, via external perfusion of non-blood solutions, and/or via tracer injection following reperfusion. Studies of focal ischemia were excluded. Data extracted included species, ischemia duration, temperature during ischemia, ischemia model, perfusate type, and perfusion quality assessment method. The perfusion quality outcome was operationalized as either the average percentage of brain tissue perfused or the percentage of brains in a group that were adequately perfused. Study quality was assessed using a custom domain-specific checklist. The review protocol was preregistered on the Open Science Framework (https://osf.io/2qm3w). Results: We included 60 studies with 192 study arms reporting on the perfusion of the brains of rabbits, rats, pigs, dogs, cats, and humans. Studies differed in the model of ischemia, the perfusate, the perfusion parameters, the quality assessment methods, and other factors. Longer ischemia was associated with lower perfusion quality, but the relationship appeared to be a gradual decline rather than a sharp threshold. Additionally, the variability across studies was large, and some studies have found that at least partial perfusion is possible after longer periods. Within-study dose-response curves were more consistent than the pooled cross-study pattern. Conclusions: How long the brain remains perfusable after circulatory arrest has not yet been definitively established. On average, perfusion quality clearly declines rapidly as the duration of global cerebral ischemia increases. However, some studies, often using interventions such as hypothermia or vasopressors, have reported at least partial perfusion of the brain even after 30 or 60 minutes of ischemia. Moreover, at least partial perfusion has been reported in human brain banking studies after postmortem intervals of several hours or days in some donors. Limitations of this review include substantial heterogeneity in study methods and outcome measures, which precluded formal meta-analysis. Future research may benefit from more thorough and precise measures of perfusion quality.