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      Cerebral Autoregulation in Subarachnoid Hemorrhage

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          Abstract

          Subarachnoid hemorrhage (SAH) is a devastating stroke subtype with a high rate of mortality and morbidity. The poor clinical outcome can be attributed to the biphasic course of the disease: even if the patient survives the initial bleeding emergency, delayed cerebral ischemia (DCI) frequently follows within 2 weeks time and levies additional serious brain injury. Current therapeutic interventions do not specifically target the microvascular dysfunction underlying the ischemic event and as a consequence, provide only modest improvement in clinical outcome. SAH perturbs an extensive number of microvascular processes, including the “automated” control of cerebral perfusion, termed “ cerebral autoregulation.” Recent evidence suggests that disrupted cerebral autoregulation is an important aspect of SAH-induced brain injury. This review presents the key clinical aspects of cerebral autoregulation and its disruption in SAH: it provides a mechanistic overview of cerebral autoregulation, describes current clinical methods for measuring autoregulation in SAH patients and reviews current and emerging therapeutic options for SAH patients. Recent advancements should fuel optimism that microvascular dysfunction and cerebral autoregulation can be rectified in SAH patients.

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          Most cited references318

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          Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association.

          The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.
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            Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease.

            The brain is critically dependent on a continuous supply of blood to function. Therefore, the cerebral vasculature is endowed with neurovascular control mechanisms that assure that the blood supply of the brain is commensurate to the energy needs of its cellular constituents. The regulation of cerebral blood flow (CBF) during brain activity involves the coordinated interaction of neurons, glia, and vascular cells. Thus, whereas neurons and glia generate the signals initiating the vasodilation, endothelial cells, pericytes, and smooth muscle cells act in concert to transduce these signals into carefully orchestrated vascular changes that lead to CBF increases focused to the activated area and temporally linked to the period of activation. Neurovascular coupling is disrupted in pathological conditions, such as hypertension, Alzheimer disease, and ischemic stroke. Consequently, CBF is no longer matched to the metabolic requirements of the tissue. This cerebrovascular dysregulation is mediated in large part by the deleterious action of reactive oxygen species on cerebral blood vessels. A major source of cerebral vascular radicals in models of hypertension and Alzheimer disease is the enzyme NADPH oxidase. These findings, collectively, highlight the importance of neurovascular coupling to the health of the normal brain and suggest a therapeutic target for improving brain function in pathologies associated with cerebrovascular dysfunction.
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              The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.

              The term spreading depolarization describes a wave in the gray matter of the central nervous system characterized by swelling of neurons, distortion of dendritic spines, a large change of the slow electrical potential and silencing of brain electrical activity (spreading depression). In the clinic, unequivocal electrophysiological evidence now exists that spreading depolarizations occur abundantly in individuals with aneurismal subarachnoid hemorrhage, delayed ischemic stroke after subarachnoid hemorrhage, malignant hemispheric stroke, spontaneous intracerebral hemorrhage or traumatic brain injury. Spreading depolarization is induced experimentally by various noxious conditions including chemicals such as potassium, glutamate, inhibitors of the sodium pump, status epilepticus, hypoxia, hypoglycemia and ischemia, but it can can also invade healthy, naive tissue. Resistance vessels respond to it with tone alterations, causing either transient hyperperfusion (physiological hemodynamic response) in healthy tissue or severe hypoperfusion (inverse hemodynamic response, or spreading ischemia) in tissue at risk for progressive damage, which contributes to lesion progression. Therapies that target spreading depolarization or the inverse hemodynamic response may potentially treat these neurological conditions.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                23 July 2021
                2021
                : 12
                : 688362
                Affiliations
                [1] 1Department of Physiology, University of Toronto , Toronto, ON, Canada
                [2] 2Toronto Centre for Microvascular Medicine at the Ted Rogers Centre for Heart Research Translational Biology and Engineering Program, University of Toronto , Toronto, ON, Canada
                [3] 3Heart & Stroke/Richard Lewar Centre of Excellence for Cardiovascular Research, University of Toronto , Toronto, ON, Canada
                Author notes

                Edited by: Xiuyun Liu, Johns Hopkins University, United States

                Reviewed by: Adel Helmy, University of Cambridge, United Kingdom; Masayo Koide, University of Vermont, United States

                *Correspondence: Steffen-Sebastian Bolz sts.bolz@ 123456utoronto.ca

                This article was submitted to Stroke, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2021.688362
                8342764
                34367053
                76d891ce-9924-401b-b2b9-6a7b47e88344
                Copyright © 2021 Lidington, Wan and Bolz.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 March 2021
                : 25 June 2021
                Page count
                Figures: 3, Tables: 8, Equations: 0, References: 318, Pages: 29, Words: 24479
                Funding
                Funded by: Heart and Stroke Foundation of Canada 10.13039/100004411
                Categories
                Neurology
                Review

                Neurology
                stroke,microvascular dysfunction,cerebral blood flow,cystic fibrosis transmembrane conductance regulator,delayed ischemia

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