Abstract
Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function.
Highlights
795,000 strokes occur in the US each year, and there are many survivors [1]
We discuss new targets including 20-Hydroxyeicosatetraenoic acid(20-HETE), Gamma-Adducin(Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the regulation of cerebral vascular function
It is generally accepted that autoregulation of Cerebral Blood Flow (CBF) is mediated by an interplay between the myogenic response in Vascular Smooth Muscle Cells (VSMCs) acting in concert with the release of vasodilatory metabolic mediators from the surrounding hypoxic brain tissue when Cerebral Perfusion Pressure (CPP) is reduced [8,9]
Summary
795,000 strokes occur in the US each year, and there are many survivors [1]. 87% of strokes are ischemic [3]. Risk factors for ischemic stroke include aging, hypertension, diabetes, obesity especially with increased waist-to-hip ratio, dyslipidemia, smoking, chronic kidney disease, and other cardiovascular diseases [4]. The mechanisms that link aging, hypertension, stroke and cognitive impairments are not fully understood. There is an urgent need to understand the pathogenesis and discover novel drug targets for prevention and treatment of these devastating diseases. In this brief review, we aim to explore the cerebral autoregulatory signal mechanism and its pathogenesis in hypertension and ischemic stroke-induced cognitive deficits. We discuss new targets including 20-Hydroxyeicosatetraenoic acid(20-HETE), Gamma-Adducin(Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the regulation of cerebral vascular function
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