Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke.
The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury after ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in blood-brain barrier integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.
From the Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia (T.M.D.S.); and Departments of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City Veterans Affairs Healthcare System (F.M.F.).
Xiaoming
X
Hu
From the Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia (T.M.D.S.); and Departments of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City Veterans Affairs Healthcare System (F.M.F.).
T Michael
TM
De Silva
From the Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia (T.M.D.S.); and Departments of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City Veterans Affairs Healthcare System (F.M.F.).
Jun
J
Chen
From the Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia (T.M.D.S.); and Departments of Internal Medicine and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City Veterans Affairs Healthcare System (F.M.F.). frank-faraci@uiowa.edu ChenJ2@upmc.edu.
Frank M
FM
Faraci
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D012307:Risk Factors; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology*
blood-brain barrier; cerebrovascular circulation; endothelium; inflammation; pericytes; risk factors