Subarachnoid Hemorrhage, Spreading Depolarizations and Impaired Neurovascular Coupling

Abstract

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.

Cerebral microcirculatory failure after subarachnoid hemorrhage is reversed by hyaluronidase

“…Additionally, the work we presented here is also consistent with the SAH Neurovascular Inversion hypothesis put forward by the Wellman Lab in that the peak severity of neurovascular inversion ($48 h) fits with the time course of microvascular disruption we observed as well as the lack of structural changes (endothelial and astrocytic swelling, perecytic constriction). 39 Our work provides further evidence that SAH causes specific disturbances of capillary blood flow that affect oxygen delivery and neuronal survival. Future work can focus on better defining the mechanical, cellular, and molecular events that conspire to cause capillary narrowing after SAH and the effects that decreased capillary blood flow has on brain function.…”

Effects of iodinated contrast media in a novel model for cerebral vasospasm

“…This observation supports clinical evidences that the autoregulation of cerebral blood flow is disturbed after SAH, what may contribute to brain damage 25 . It has been shown that pressurized arteries from rabbits where SAH had been induced in vivo have enhanced myogenic response 26 .…”

“…By careful and controlled isolation of each vessel we can also exclude that vessel dysfunction happens due to mechanical damage by bleeding. Although mechanical irritation of vessels or brain damage are considered as possible contributing factors 4,8,24,25 to clinical vasospasm, in our study we intended to separate the mechanical effects from the effects of blood clot presence and ageing.…”

“…This is important because patients with SAH have disturbances of cerebral blood regulation 25 , and many diagnostic and therapeutic procedures needed for their treatment may require the use of CM 12,13,14 . It has been shown that several types of CM may have potentially deleterious effects on the tone and reactivity of vessels from several vascular beds 15,16 .…”

Purinergic signaling triggers endfoot high-amplitude Ca2+ signals and causes inversion of neurovascular coupling after subarachnoid hemorrhage

“…In brain slices from SAH model animals, however, the polarity of the vascular response to neuronal activation is shifted from vasodilation to vasoconstriction. 15,16 This inversion of NVC may contribute to the development of focal ischemia after SAH by restricting blood flow to active brain regions. Recent evidence indicates that altered astrocyte Ca 2þ signaling in the form of the emergence of spontaneous endfoot high-amplitude Ca 2þ signals (eHACSs) is associated with SAH-induced inversion of NVC.…”