الفهرس 
The Neurovascular UnitOnly 14 pages are availabe for public view
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Abstract
The “neurovascular unit” is an emerging concept that emphasizes the interactions among different types of cells in the brain, including neuronal, glial, perivascular and vascular elements. These cells are closely interrelated and work in concert to maintain the homeostaticsignaling of normal brain function.
A growing body of evidence indicates that neurons, glia (astrocytes, microglia, oligodendrocytes) and vascular cells (endothelium, smooth muscle cells or pericytes, adventitial cells) are closely related developmentally, structurally, and functionally. The term “neurovascular unit” was introduced to highlight the intimate functional relationships between these cells and their coordinated pattern of reaction to injury.
The function of the neurovascular unit is to regulate blood flow, control the exchange across the blood brain barrier, contribute to immune surveillance in the brain, and provide trophic support to brain cells.
Homeostatic signaling within the neurovascular unit underlies normal brain function. Hemodynamic coupling between neurons and the cerebrovasculature mediates the cerebral blood flow response to neuronal activation. Cell-cell interactions between astrocytes and endothelial cells sustainthe functionality of the blood-brain barrier. Neurotransmittertrafficking between neuronal release and glial reuptake modulates the kinetics of neurotransmission.
There is increasing evidence that cerebrovascular dysfunction plays a role not only in vascularcauses of cognitive impairment but also in Alzheimer’s disease (AD). The structure and function of the neurovascular unit are profoundly impaired in VCI and AD. Injury to the neurovascular unit alters cerebral blood flow regulation, depletes vascular reserves, disrupts the blood brain barrier, and reduces the brain’s repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. Vascular oxidative stress and inflammation are key pathogenic factors in neurovascular dysfunction.
Instead of considering Vascular Dementia (VaD) a pure result of neuronal death and the interruption of neuronal networks that support cognitive function, we hypothesize that early brain malfunction is induced by vascular risk factors and chronic hypoxia. A reduction of cerebral blood flow and a series of molecular events precede the major ischemic events in vascular cognitive impairment.
Vascular damage (reduced blood perfusion of the brain and brain hypoxia, BBB dysfunction or both) occurs initially and leads to neurodegenerative changes, accumulation of Aβ and faulty clearance of Aβ. Aβ can then amplify the neurovascular dysfunction through the development of amyloid angiopathy, potentiating blood flow dysfunction and vascular-mediated neuronal injury and neurodegeneration.
Considering that modifiable vascular risk factors can be controlled, approaches to treat dementia should rely heavily on strategies to preserve cerebrovascular health. In support of this approach, treatment of vascular risk factors in AD patients slows down the cognitive decline. A healthy diet and exercise can help minimize the deleterious effects of cardiovascular risk factors and have a positive effect oncognition. In the absence of specific interventions targeting the mechanisms of vascular or neurodegenerative dementia, lifestyle modification and risk factor control may be valuable initial steps to mitigate the cognitive decline associated both with AD and VCI.
Current therapies aimed at correcting neuron function have had limited success in treating CNS disease. Managing symptoms with medication in the early stages of disease can be effective. Yet, disease progression often leads to the use of higher doses of medication with unwanted side effects or the medication may no longer be helpful for symptom management. Targeting the NVU, which has primarily focused upon the vasculature, has had some success with treating or limiting CNS disease progression.
The early molecular changes within the neurovascular pathway may offer new therapeutic targets for controlling progression of dementia in AD, including therapies based on receptors RAGE and LRP and/or on genes implicated in the neurovascular AD model, such as mesenchyme homebox gene 2 (MEOX2) and myocardin (MYOCD).
There are two drug classes with reported benefits on brain hemodynamics and neurovascular coupling in AD patients which are cholinesterase inhibitors and peroxisome proliferator-activated receptor γ agonists.