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      Structural and Functional Remodeling of the Brain Vasculature Following Stroke

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          Abstract

          Maintenance of cerebral blood vessel integrity and regulation of cerebral blood flow ensure proper brain function. The adult human brain represents only a small portion of the body mass, yet about a quarter of the cardiac output is dedicated to energy consumption by brain cells at rest. Due to a low capacity to store energy, brain health is heavily reliant on a steady supply of oxygen and nutrients from the bloodstream, and is thus particularly vulnerable to stroke. Stroke is a leading cause of disability and mortality worldwide. By transiently or permanently limiting tissue perfusion, stroke alters vascular integrity and function, compromising brain homeostasis and leading to widespread consequences from early-onset motor deficits to long-term cognitive decline. While numerous lines of investigation have been undertaken to develop new pharmacological therapies for stroke, only few advances have been made and most clinical trials have failed. Overall, our understanding of the acute and chronic vascular responses to stroke is insufficient, yet a better comprehension of cerebrovascular remodeling following stroke is an essential prerequisite for developing novel therapeutic options. In this review, we present a comprehensive update on post-stroke cerebrovascular remodeling, an important and growing field in neuroscience, by discussing cellular and molecular mechanisms involved, sex differences, limitations of preclinical research design and future directions.

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          Most cited references351

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          Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes.

          Stroke has a greater effect on women than men because women have more events and are less likely to recover. Age-specific stroke rates are higher in men, but, because of their longer life expectancy and much higher incidence at older ages, women have more stroke events than men. With the exception of subarachnoid haemorrhage, there is little evidence of sex differences in stroke subtype or severity. Although several reports found that women are less likely to receive some in-hospital interventions, most differences disappear after age and comorbidities are accounted for. However, sex disparities persist in the use of thrombolytic treatment (with alteplase) and lipid testing. Functional outcomes and quality of life after stroke are consistently poorer in women, despite adjustment for baseline differences in age, prestroke function, and comorbidities. Here, we comprehensively review the epidemiology, clinical presentation, medical care, and outcomes of stroke in women.
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            Stroke in the 21 st Century: A Snapshot of the Burden, Epidemiology, and Quality of Life

            Stroke is ranked as the second leading cause of death worldwide with an annual mortality rate of about 5.5 million. Not only does the burden of stroke lie in the high mortality but the high morbidity also results in up to 50% of survivors being chronically disabled. Thus stroke is a disease of immense public health importance with serious economic and social consequences. The public health burden of stroke is set to rise over future decades because of demographic transitions of populations, particularly in developing countries. This paper provides an overview of stroke in the 21st century from a public health perspective.
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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 Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                07 August 2020
                2020
                : 11
                : 948
                Affiliations
                [1] 1Neuroscience Program, Ottawa Hospital Research Institute , Ottawa, ON, Canada
                [2] 2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa , Ottawa, ON, Canada
                [3] 3Brain and Mind Research Institute, University of Ottawa , Ottawa, ON, Canada
                Author notes

                Edited by: Fabrice Dabertrand, University of Colorado School of Medicine, United States

                Reviewed by: William J. Pearce, Loma Linda University School of Medicine, United States; Anne Dorrance, Michigan State University, United States

                *Correspondence: Baptiste Lacoste, blacoste@ 123456uottawa.ca

                This article was submitted to Vascular Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2020.00948
                7433746
                32848875
                a0a24e84-c1a3-42ad-9380-3aa3ee4d80f4
                Copyright © 2020 Freitas-Andrade, Raman-Nair and Lacoste.

                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
                : 11 May 2020
                : 14 July 2020
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 458, Pages: 28, Words: 0
                Funding
                Funded by: Heart and Stroke Foundation of Canada 10.13039/100004411
                Categories
                Physiology
                Review

                Anatomy & Physiology
                stroke,cerebrovascular,neurovascular unit,vascular remodeling,angiogenesis,blood–brain barrier

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