Cerebral artery myogenic reactivity: The next frontier in developing effective interventions for subarachnoid hemorrhage

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating cerebral event that kills or debilitates the majority of those afflicted. The blood that spills into the subarachnoid space stimulates profound cerebral artery vasoconstriction and consequently, cerebral ischemia. Thus, once the initial bleeding in SAH is appropriately managed, the clinical focus shifts to maintaining/improving cerebral perfusion. However, current therapeutic interventions largely fail to improve clinical outcome, because they do not effectively restore normal cerebral artery function. This review discusses emerging evidence that perturbed cerebrovascular "myogenic reactivity," a crucial microvascular process that potently dictates cerebral perfusion, is the critical element underlying cerebral ischemia in SAH. In fact, the myogenic mechanism could be the reason why many therapeutic interventions, including "Triple H" therapy, fail to deliver benefit to patients. Understanding the molecular basis for myogenic reactivity changes in SAH holds the key to develop more effective therapeutic interventions; indeed, promising recent advancements fuel optimism that vascular dysfunction in SAH can be corrected to improve outcome.

Antioxidant Melatonin: Potential Functions in Improving Cerebral Autoregulation After Subarachnoid Hemorrhage

“…The control of arterial myogenic tone was first described by Bayliss (1902) . The myogenic response was regulated by a complex mechanism, and some of these mechanisms are out of balance after SAH ( Lidington et al, 2018 ). (1) Previous study reported that potassium channels are important regulators of vascular tone.…”

“…(2) After SAH, endothelial dysfunction was observed, resulting in reduced vasodilating factors levels. Thus, it is reasonable to speculate that endothelial dysfunction augments myogenic response disorder ( Lidington et al, 2018 ). (3) The effect of ROS on myogenic response disorder was our concern.…”

Review of studies on dynamic cerebral autoregulation in the acute phase of stroke and the relationship with clinical outcome

“…The aim of this article is to perform a narrative review of observational studies that assessed dCA in acute ischemic and haemorrhagic stroke patients, with a special focus on the relationship between dCA status and clinical outcome measures. Although, in the literature, there are several publications reviewing dCA in stroke, 20,28–35 the present review is distinct from the others as the focus is on the studies that evaluated patients in the acute phase (<48hs) after stroke onset. The INFOMATAS group believes that one of the core issues to be understood is whether cerebral hemodynamics in the acute phase is impaired and consequently impacts clinical outcome.…”

Targeting Muscles in the Brain to Enhance Cerebral Perfusion

“…Previous work from Lidington et al. (5) has shown a remarkable similarity between cerebrovascular mechanisms leading to DCI after SAH and that observed after chronic HF in rodent experimental models. These studies have shown enhanced cerebrovascular myogenic response due to decreased CFTR expression, reversible by blocking TNF-α signaling.…”