Role of astrocytes in cerebrovascular regulation

Abstract

Astrocytes send processes to synapses and blood vessels, communicate with other astrocytes through gap junctions and by release of ATP, and thus are an integral component of the neurovascular unit. Electrical field stimulations in brain slices demonstrate an increase in intracellular calcium in astrocyte cell bodies transmitted to perivascular end-feet, followed by a decrease in vascular smooth muscle calcium oscillations and arteriolar dilation. The increase in astrocyte calcium after neuronal activation is mediated, in part, by activation of metabotropic glutamate receptors. Calcium signaling in vitro can also be influenced by adenosine acting on A2B receptors and by epoxyeicosatrienoic acids (EETs) shown to be synthesized in astrocytes. Prostaglandins, EETs, arachidonic acid, and potassium ions are candidate mediators of communication between astrocyte end-feet and vascular smooth muscle. In vivo evidence supports a role for cyclooxygenase-2 metabolites, EETs, adenosine, and neuronally derived nitric oxide in the coupling of increased blood flow to increased neuronal activity. Combined inhibition of the EETs, nitric oxide, and adenosine pathways indicates that signaling is not by parallel, independent pathways. Indirect pharmacological results are consistent with astrocytes acting as intermediaries in neurovascular signaling within the neurovascular unit. For specific stimuli, astrocytes are also capable of transmitting signals to pial arterioles on the brain surface for ensuring adequate inflow pressure to parenchymal feeding arterioles. Therefore, evidence from brain slices and indirect evidence in vivo with pharmacological approaches suggest that astrocytes play a pivotal role in regulating the fundamental physiological response coupling dynamic changes in cerebral blood flow to neuronal synaptic activity. Future work using in vivo imaging and genetic manipulation will be required to provide more direct evidence for a role of astrocytes in neurovascular coupling.

Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs

“…Astrocytes are the most abundant cell type in the higher mammalian brain. Parenchymal arterioles are ensheathed by astrocyte end-feet (15,25), and pial arterioles are coated by astrocyte processes and end feet (present study). Astrocytes can act as intermediaries between neurons and cerebral blood vessels in regulation of cerebral vascular tone in response to neuronal activity, thereby adjusting cerebral blood flow to metabolism (15,25).…”

“…They function as intermediaries between neurons and cerebral arterioles in regulation of cerebral vascular tone in response to neuronal activity, thereby adjusting cerebral blood flow to metabolism (15,25). Whether astrocytes are involved in dilation in response to glutamate released at excitatory synapses and the nature of astrocyte-derived vasodilator(s) employed remain uncertain.…”

The cellular response in neuroinflammation: The role of leukocytes, microglia and astrocytes in neuronal death and survival

“…For example, astrocytes play a critical role in modulating glutamate levels in the extracellular space contributing both to the functional neuronal synapse and to the prevention of glutamate-induced excitotoxic cell death of neurons [23,27,28]. In addition, astrocyte endfeet are a key component of the blood brain barrier (BBB) [29][30][31]. In vitro data suggest that astrocyte interactions with the cerebrovasculature endothelium play a key role in the induction and maintenance of the tight junctions characteristic of the intact BBB.…”

“…In vitro data suggest that astrocyte interactions with the cerebrovasculature endothelium play a key role in the induction and maintenance of the tight junctions characteristic of the intact BBB. Furthermore, astrocyte production of pro-inflammatory cytokines such as TNFα play key roles in facilitating leukocyte extravasation from the bloodstream across the BBB into the CNS parenchyma [29][30][31][32]. Lastly, it is largely unexplored to what extent the many homeostatic functions of astrocytes such as the buffering of pH and glutamate are significantly altered by their cellular transition into "reactive" astrocytes.…”

Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

“…Thus, it is possible that the cholinergic cells may modulate blood vessel diameter via pericytes to modulate blood flow, though further investigation is needed to confirm this. Several recent studies also indicate that glial cells can act as intermediaries in signaling from neurons to blood vessels [25,51]. These interactions can be disrupted during retinal disease, which provides a strong impetus for future studies to characterize the retinal neurovascular unit.…”