Neurovascular unit

The neurovascular unit (NVU) comprises the components of the brain that collectively regulate cerebral blood flow in order to deliver the requisite nutrients to activated neurons.[1] 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 substrates for energy metabolism–mainly glucose–in specific areas, quantities, and times.[2] Neurons do not have the same ability as, for example, muscle cells, which can use up their energy reserves and refill them later; therefore, cerebral metabolism must be driven in the moment. The neurovascular unit facilitates this ad hoc delivery and, thus, ensures that neuronal activity can continue seamlessly.[2]

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).[1] 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.[1]

The neurovascular unit consists of neurons, astrocytes, vasculature (endothelial and vascular mural cells), the vasomotor apparatus (smooth muscle cells and pericytes), and microglia.[1] Together these function in the homeostatic haemodynamic response of cerebral hyperaemia.[3] Cerebral hyperaemia is a fundamental central nervous system mechanism of homeostasis that increases blood supply to neural tissue when necessary.[3] This mechanism controls oxygen and nutrient levels using vasodilation and vasoconstriction in a multidimensional process involving the many cells of the neurovascular unit, along with multiple signaling molecules.[1] The interactions between the components of the NVU allow it to sense neurons' needs of oxygen and glucose and, in turn, trigger the appropriate vasodilatory or vasoconstrictive responses.[3] Neuronal activity[4] as well as astrocytes[5] can therefore participate in CNV, both by inducing vasodilation and vasoconstriction[6].Thus, the NVU provides the architecture behind neurovascular coupling, which connects neuronal activity to cerebral blood flow and highlights the interdependence of their development, structure, and function.[1]

A schematic of the neurovascular unit (NVU), where astrocyte processes surround the capillary basement membrane and pericytes, creating the glia limitans. Also, resident in the perivascular space are antigen-presenting cells (APCs) and border-associated macrophages (BAMs).

The temporal and spatial link between cerebral blood flow and neuronal activity allows the former to serve as a proxy for the latter. 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.[1] Imaging of the brain also allows researchers to better understand the neurovascular unit and its many complexities. Furthermore, any impediments to the function of the neurovascular system will prevent neurons from receiving the appropriate nutrients. A complete stoppage for only a few minutes, which could be caused by arterial occlusion or heart failure, can result in permanent damage and death. Dysfunction in the NVU is also associated with neurodegenerative diseases including Alzheimer's and Huntington's disease.[1]

  1. ^ a b c d e f g h Iadecola C (September 2017). "The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease". Neuron. 96 (1): 17–42. doi:10.1016/j.neuron.2017.07.030. PMC 5657612. PMID 28957666.
  2. ^ a b Stackhouse TL, Mishra A (2021-07-12). "Neurovascular Coupling in Development and Disease: Focus on Astrocytes". Frontiers in Cell and Developmental Biology. 9: 702832. doi:10.3389/fcell.2021.702832. PMC 8313501. PMID 34327206.
  3. ^ a b c Muoio V, Persson PB, Sendeski MM (April 2014). "The neurovascular unit - concept review". Acta Physiologica. 210 (4): 790–798. doi:10.1111/apha.12250. PMID 24629161. S2CID 25274791.
  4. ^ Cauli B, Tong XK, Rancillac A, Serluca N, Lambolez B, Rossier J, et al. (October 2004). "Cortical GABA interneurons in neurovascular coupling: relays for subcortical vasoactive pathways". The Journal of Neuroscience. 24 (41): 8940–8949. doi:10.1523/JNEUROSCI.3065-04.2004. PMC 6730057. PMID 15483113. The expression of vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) in interneurons induces dilation, while somatostatin (SOM) induces contraction. Direct perfusion of VIP and NO donors onto the slices caused microvessel dilation, whereas neuropeptide Y (NPY) and SOM induced vasoconstriction. Vasomotor interneurons established contacts with local microvessels and received somatic and dendritic afferents from acetylcholine (ACh) and serotonin (5-HT) pathways, varying by interneuron subtype. Our results demonstrate the capability of specific subsets of cortical GABA interneurons to transmute neuronal signals into vascular responses and suggest that they could serve as local integrators of neurovascular coupling for subcortical vasoactive pathways.
  5. ^ Carmignoto G, Gómez-Gonzalo M (May 2010). "The contribution of astrocyte signalling to neurovascular coupling". Brain Research Reviews. 63 (1–2): 138–148. doi:10.1016/j.brainresrev.2009.11.007. PMID 19948187.
  6. ^ Rancillac A, Rossier J, Guille M, Tong XK, Geoffroy H, Amatore C, et al. (June 2006). "Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum". The Journal of Neuroscience. 26 (26): 6997–7006. doi:10.1523/JNEUROSCI.5515-05.2006. PMC 6673912. PMID 16807329. Cerebellar stellate and Purkinje cells play distinct roles in neurovascular coupling by dilating and constricting neighboring microvessels, respectively. This highlights the specialized functions of different neuron types in regulating cerebral blood flow.