Neuroprotection in ischemic stroke: AhR we making progress?

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Cerebrovascular accidents, more commonly referred to as strokes, remain the second most common cause of mortality and the third most common cause of disability worldwide.1 It has been estimated that more than three quarters of all strokes in the United States are attributable to ischemia, with the remainder principally related to intracranial hemorrhage.2,3 Although our attempts to address modifiable risk factors for stroke have decreased the incidence of stroke, stroke-related death and disability are increasing at concerning rates.4,5 These observations lie in stark contrast to contemporary metrics for acute myocardial infarction, for which both short-term mortality and long-term mortality have been decreasing over the past 30 years,6,7 concomitant with the increasing use of prompt reperfusion strategies, including primary percutaneous coronary intervention. The cell types affected in the context of stroke and myocardial infarction (neurons and cardiomyocytes, respectively) are similar in that both are terminally differentiated cells that are exquisitely sensitive to ischemic insults. Following the adage that “time is brain” in the setting of acute ischemic stroke, the benefit of restoring blood flow with thrombolytic therapy decreases in a continuous fashion over time, with studies demonstrating that each 15-minute delay in the time to initiation of therapy is associated with reduced odds of independent ambulation and survival.8,9 However, compared with coronary revascularization, the temporal window for safe and effective cerebral reperfusion therapy is exceedingly narrow and complicated by the challenges associated with identifying stroke symptoms and obtaining rapid …