Two decades of astrocytes in neurovascular coupling

Abstract

The brain is a highly energy demanding organ, which accounts in humans for the 20% of total energy consumption at resting state although comprising only 2% of the body mass. The necessary delivery of nutrients to brain parenchyma is ensured by the cerebral circulatory system, through the exchange of glucose and oxygen (O2) at the capillary level. Notably, a tight spatial and temporal correlation exists between local increases in neuronal activity and the subsequent changes in regional cerebral blood flow. The recognized concept of neurovascular coupling (NVC), also named functional hyperemia, expresses this close relationship and stands at the basis of the modern functional brain imaging techniques. Different cellular and molecular mechanisms have been proposed to mediate this tight coupling. In this context, astrocytes are ideally positioned to act as relay elements that sense neuronal activity through their perisynaptic processes and release vasodilator agents at their endfeet in contact with brain parenchymal vessels. Two decades after the astrocyte involvement in neurovascular coupling has been proposed, we here review the experimental evidence that contributed to unraveling the molecular and cellular mechanisms underlying cerebral blood flow regulation. While traveling through the different controversies that moved the research in this field, we keep a peculiar focus on those exploring the role of astrocytes in neurovascular coupling and conclude with two sections related to methodological aspects in neurovascular research and to some pathological conditions resulting in altered neurovascular coupling.

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states

“…4c and d), suggesting that the generator(s) for seizure-associated ISOs and rCBV oscillations may share a common mechanism. Due to their ability to generate slow, seizure-related DC shifts 19 and their role in mediating NVC responses 20 astroglia cells may contribute significantly to the observed responses and deserve further investigation. In this regard, our technological approach might allow future dissection of pathways which result in this form of activity and provide insight into seizure genesis with important therapeutic implications particularly for spontaneous seizures.…”

A systematic review of the neuropathology and memory decline induced by monosodium glutamate in the Alzheimer’s disease-like animal model

“…If high glutamate concentrations in the synaptic cleft persisted, the glutamatergic receptors on different parts of the cell, such as the dendritic spines and dendrites itself, would be tonic-activated ( Nimgampalle et al, 2023 ; Orlando et al, 2023 ; Piniella and Zafra, 2023 ). The fast and efficient clearance of glutamate from the extracellular space following neuronal activity is, therefore, necessary for the spatial and temporal limitation of neuronal activation ( Haj-Yasein et al, 2015 ; Lia et al, 2023 ). The hallmark pathologies of this illness, including amyloid-β buildup, tau hyperphosphorylation, and neuronal death, are brought on by increased intracellular calcium ( Jadiya et al, 2023 ; Mahaman et al, 2023 ).…”

Imaging the neurovascular unit in health and neurodegeneration: a scoping review of interdependencies between MRI measures

“…The vessel's continuous delivery of blood is essential for meeting the metabolic demands of neural activity and supporting all brain structures. Blood flow in the brain is moderated by multiple adaptive processes in the NVU including endothelial cell-and pericyte-facilitated vasodilation and vasoconstriction [7,8], microglial activity [9] and astrocyte-mediated neurovascular coupling [10]. Hypoperfusion, or decreased cerebral blood flow (CBF), has been associated with accelerated cognitive decline, increased risk of dementia conversion and greater Alzheimer's disease biomarker severity [11][12][13].…”