Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review
William Dodd, Dimitri Laurent, Aaron S. Dumont, David Hasan, Pascal Jabbour, Robert M. Starke, Koji Hosaka, Adam Polifka, Brian L. Hoh, Nohra Chalouhi
Abstract
Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years of investigation and clinical trials. Modern advances in basic science have produced a much more complex, multifactorial framework in which delayed cerebral ischemia is better understood and novel treatments can be developed. Leveraging this knowledge to improve outcomes, however, depends on a holistic understanding of the disease process. We conducted a review of the literature to analyze the current state of investigation into delayed cerebral ischemia with emphasis on the major themes that have emerged over the past decades. Specifically, we discuss microcirculatory dysfunction, glymphatic impairment, inflammation, and neuroelectric disruption as pathological factors in addition to the canonical focus on cerebral vasospasm. This review intends to give clinicians and researchers a summary of the foundations of delayed cerebral ischemia pathophysiology while also underscoring the interactions and interdependencies between pathological factors. Through this overview, we also highlight the advances in translational studies and potential future therapeutic opportunities.