The brain has high metabolic and energy needs and requirescontinuous cerebral blood flow (CBF), which is facilitatedby a tight coupling between neuronal activity, CBF,and metabolism. Upon neuronal activation, there is an increasein energy demand, which is then met by a hemodynamicresponse that increases CBF. Such regional CBFincrease in response to neuronal activation is observedusing neuroimaging techniques such as functional magneticresonance imaging and positron emission tomography.The mechanisms and mediators (eg, nitric oxide, astrocytes,and ion channels) that regulate CBF-metabolismcoupling have been extensively studied. The neurovascularunit is a conceptual model encompassing the anatomicaland metabolic interactions between the neurons,vascular components, and glial cells in the brain. It is compromisedunder disease states such as stroke, diabetes, hypertension,dementias, and with aging, all of which triggera cascade of inflammatory responses that exacerbatebrain damage. Hence, tight regulation and maintenanceof neurovascular coupling is central for brain homeostasis.This review article also discusses the waste clearance pathwaysin the brain such as the glymphatic system. The glymphaticsystem is a functional waste clearance pathwaythat removes metabolic wastes and neurotoxins from thebrain along paravascular channels. Disruption of the glymphaticsystem burdens the brain with accumulating wasteand has been reported in aging as well as several neurologicaldiseases.
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