Aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences on brain function including profound effects on communication between neurons and the vasculature leading to cerebral ischemia. Physiologically, neurovascular coupling represents a focal increase in cerebral blood flow to meet increased metabolic demand of neurons within active regions of the brain. Neurovascular coupling is an ongoing process involving coordinated activity of the neurovascular unit—neurons, astrocytes, and parenchymal arterioles. Neuronal activity can also influence cerebral blood flow on a larger scale. Spreading depolarizations (SD) are self-propagating waves of neuronal depolarization and are observed during migraine, traumatic brain injury, and stroke. Typically, SD is associated with increased cerebral blood flow. Emerging evidence indicates that SAH causes inversion of neurovascular communication on both the local and global level. In contrast to other events causing SD, SAH-induced SD decreases rather than increases cerebral blood flow. Further, at the level of the neurovascular unit, SAH causes an inversion of neurovascular coupling from vasodilation to vasoconstriction. Global ischemia can also adversely affect the neurovascular response. Here, we summarize current knowledge regarding the impact of SAH and global ischemia on neurovascular communication. A mechanistic understanding of these events should provide novel strategies to treat these neurovascular disorders. 1. Pathophysiology of Subarachnoid Hemorrhage Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality with limited therapeutic options [1]. The major contributor to poor outcome of patients surviving the initial surge in intracranial pressure is delayed cerebral ischemia (DCI) manifesting 4–10 days after aneurysm rupture as new and otherwise unexplained neurological deficits and/or ischemic lesions within the brain [2]. Despite decades of study, mechanisms contributing to SAH-induced DCI remain controversial. For many years, a delayed and prolonged vasospasm of large conduit arteries was thought to be the major contributor to DCI and the ensuing death and disability observed in SAH patients [3, 4]. Recent data, however, challenge this view [5–7] and strongly suggest that additional mechanisms contribute to poor outcomes after SAH, including early brain injury suffered at the time of bleed [6, 8–10], blood-brain barrier disruption [11, 12], inflammation [13–15], and impaired microcirculatory function [16–19]. Evidence suggests that a pathological inversion of
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