The neurovascular unit - concept review

Abstract

The cerebral hyperaemia is one of the fundamental mechanisms for the central nervous system homeostasis. Due also to this mechanism, oxygen and nutrients are maintained in satisfactory levels, through vasodilation and vasoconstriction. The brain hyperaemia, or coupling, is accomplished by a group of cells, closely related to each other; called neurovascular unit (NVU). The neurovascular unit is composed by neurones, astrocytes, endothelial cells of blood-brain barrier (BBB), myocytes, pericytes and extracellular matrix components. These cells, through their intimate anatomical and chemical relationship, detect the needs of neuronal supply and trigger necessary responses (vasodilation or vasoconstriction) for such demands. Here, we review the concepts of NVU, the coupling mechanisms and research strategies.

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

“…NVU comprises vascular cells (endothelial cells), perivascular constituents of the blood-brain barrier (pericytes and astrocytes) and their associated neurons, as well as extracellular matrix components [112]. NVU also includes microglial cells, vascular smooth muscle cells located around blood vessels, specialized cellular compartments such as the endothelial glycocalyx, the endothelial lining of cerebral capillaries, capillary tight junctions, and the capillary basement membrane [113].…”

“…NVU also includes microglial cells, vascular smooth muscle cells located around blood vessels, specialized cellular compartments such as the endothelial glycocalyx, the endothelial lining of cerebral capillaries, capillary tight junctions, and the capillary basement membrane [113]. Together, the components of NVU detect physiological needs of the neural tissue and respond accordingly to supply these demands [112]. Consequently, under normal conditions, cerebral blood flow is maintained constant despite wide changes in perfusion pressure [114], a phenomenon called autoregulation of cerebral blood flow [115].…”

Permeability imaging in cerebrovascular diseases: applications and progress in research

“…It is important to pay more attention to the dynamic changes in the neurovascular units (NVU), which are the integrative microunits of structure and function of the nervous system. Thus, neurons, endothelial cells, astrocytes, and the extracellular matrix that maintains the integrity of the brain tissue need to be viewed comprehensively, with the BBB acting as the core of the NVU [7]. The negative results from clinical trials of neuro-protective drugs also support this idea, making the NVU an important therapeutic target in future clinical research.…”

On the role of the extracellular space on the holistic behavior of the brain

“…Thus, NVU was defined by Harder et al (2002) as a structure formed by neurons, inter-neurons, microglia, astrocytes, basal lamina covered with smooth muscular cells and pericytes, endothelial cells, and the ECM. Each component fulfills its own special task but thanks to strong and reciprocal interactions among the components, the NVU operates as an anatomical and functional device allowing a highly efficient regulation of the local cerebral blood flow (Muoio et al, 2014). This interplay between different cell types is made possible by gap junctions, adhesion molecules (such as cadherins and integrins), and ionic channels (such as Ca 2+ and K + channels), as well as VT signals (such as glutamate and ATP) (Duchemin et al, 2012).…”

“…Thus, the endfoots provide a broad surface contact with both these cell types, wrapping them and acting as a fast and efficient surface for the exchange of signals. Therefore, astrocytes could act as versatile organizers of the NVU allowing the proper VT and WT communications between neurons and other NVU components, in particular, blood vessels (see references in Muoio et al, 2014). As Nedergaard points out, arrays of astrocyte-delimited micro-domains along the capillary microvasculature allow the formation of higher order gliovascular units, which serve to match local neural activity and blood flow while regulating neuronal firing thresholds through coordinative glial signaling (Nedergaard et al, 2003).…”