The neurovascular unit (NVU) comprises the components of the brain that collectively regulate cerebral blood flow in order to deliver the necessary nutrients to activated neurons. The NVU addresses the brain's unique dilemma of having high energy demands yet low energy storage capacity. In order to function properly, the brain must receive glucose for energy metabolism in specific areas, quantities, and times. Unlike muscle cells, which can deplete and later replenish their energy reserves, neurons require a continuous, real-time supply of energy. The neurovascular unit facilitates this delivery as needed, ensuring that cerebral metabolism is sustained and neuronal activity can continue seamlessly. The neurovascular unit consists of neurons, astrocytes, vasculature (endothelial and vascular mural cells), the vasomotor apparatus (smooth muscle cells and pericytes), and microglia. Together, these function in the homeostatic haemodynamic response of cerebral hyperaemia. Cerebral hyperaemia is a fundamental central nervous system homeostatic mechanism that increases blood supply to neural tissue when necessary. This mechanism regulates local perfusion through a multidimensional process involving the various cells of the neurovascular unit and signaling molecules. By interacting, these components of the NVU sense the neurons' needs for oxygen and glucose and trigger the appropriate vasodilatory or vasoconstrictive responses. Through this process, known as neurovascular coupling, neurons and astrocytes can modulate cerebral blood flow. Thus, the NVU provides the structural and cellular framework underlying neurovascular coupling, linking neuronal activity to cerebral blood flow and reflecting the interdependence of their development, structure, and function.
The neurovascular unit was formalized as a concept in 2001, at the inaugural Stroke Progress Review Group of the National Institute of Neurological Disorders and Stroke (NINDS). In prior years, the importance of both neurons and cerebral vasculature was well known; however, their interconnected relationship was not. The two were long considered distinct entities which, for the most part, operated independently. Since 2001, though, the rapid increase of scientific papers citing the neurovascular unit represents the growing understanding of the interactions that occur between the brain's cells and blood vessels. Due to the tight temporal and spatial coupling of cerebral blood flow to neuronal activity, measuring blood flow serves as an accurate proxy for brain function. Neuroimaging techniques that directly or indirectly monitor blood flow, such as fMRI and PET scans, can thus measure and locate activity in the brain with precision. Imaging of the brain also allows researchers to better understand the neurovascular unit and its many complexities. The neurons' dependence on continuous blood flow additionally makes them highly vulnerable to vascular disruptions. Any impediments that prevent neurons from receiving the appropriate nutrients can cause an array of neurological pathologies. For example, a complete stoppage for only a few minutes, potentially caused by arterial occlusion or heart failure, can result in permanent neuronal damage and cell death. Dysfunction in the NVU is also associated with neurodegenerative diseases including Alzheimer's and Huntington's disease.
Function
Anatomical components The neurovascular unit consists of vascular cells (including endothelium, pericytes, and smooth muscle cells), glia (astrocytes and microglia), and neurons with synaptic junctions for signaling. The cerebral vascular network consists of surface pial arteries that branch into penetrating arterioles within the brain parenchyma. Surrounding these vessels is the perivascular compartment, which houses immune and scavenger cells such as perivascular macrophages, Mato cells, pial cells, and mast cells. Cerebral blood flow through this system is facilitated by the major neck arteries. Segmented vascular resistance, or the amount of flow control that each section of the brain maintains, is measured as the ratio of the blood pressure gradient to blood flow volume. The vascular network within the NVU acts as a low-resistance channel that allows blood to be distributed to different parts of the brain. Within this system, the cells of the NVU sense the metabolic needs of neural tissue and release mediators that trigger the vascular smooth muscle cells to alter blood flow through vasodilation or vasoconstriction. Additionally, smooth muscle cells regulate flow via effector systems such as the myogenic effect, an inherent mechanical response where they constrict or dilate based on changes in intravascular pressure. Together, this is recognized as a multidimensional response that operates across the cerebrovascular network as a whole.
Blood–brain barrier The cells of the neurovascular unit also collectively form the blood–brain barrier (BBB), which plays an essential role in maintaining the microenvironment of the brain. The blood–brain barrier is a highly selective semipermeable membrane that controls the transport of ions, molecules, and cells between the blood and the central nervous system. The barrier strictly filters out neurotoxins and pathogens that may cause inflammation, injury, or disease, while mediating the active transport of nutrients. Encompassed within the BBB are specialized endothelial cells, pericytes, a capillary basement membrane, and astrocyte endfeet. Endothelial cells line the interior vessels and form tight junctions to restrict permeability. The tight junctions serve as the main impediment to drug delivery in the brain. Pericytes exist on the abluminal surface of this endothelial layer and are embedded within the basement membrane. They release signaling factors that determine the number of endothelial tight junctions to maintain the structural integrity and permeability of the barrier. A reduction in pericytes directly correlates with a loss of these tight junctions, leading to increased barrier permeability. Similarly, astrocytes secrete growth factors that directly induce endothelial tight junctions, and they also metabolize blood glucose into lactate for neuronal energy.
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