Role of astrocytes in cerebrovascular regulation

Raymond C Koehler, Debebe Gebremedhin, David R. Harder

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)307-317
Number of pages11
JournalJournal of Applied Physiology
Volume100
Issue number1
DOIs
StatePublished - Jan 2006

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Astrocytes
Adenosine
Calcium Signaling
Arterioles
Vascular Smooth Muscle
Cerebrovascular Circulation
Nitric Oxide
Brain
Pharmacology
Calcium
Metabotropic Glutamate Receptors
Gap Junctions
Cyclooxygenase 2
Arachidonic Acid
Synapses
Electric Stimulation
Prostaglandins
Blood Vessels
Dilatation
Potassium

Keywords

  • Adenosine
  • Cerebral blood flow
  • Epoxyeicosatrienoic acid
  • Neuronal activation
  • Nitric oxide
  • Prostaglandin

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Role of astrocytes in cerebrovascular regulation. / Koehler, Raymond C; Gebremedhin, Debebe; Harder, David R.

In: Journal of Applied Physiology, Vol. 100, No. 1, 01.2006, p. 307-317.

Research output: Contribution to journalArticle

Koehler, Raymond C ; Gebremedhin, Debebe ; Harder, David R. / Role of astrocytes in cerebrovascular regulation. In: Journal of Applied Physiology. 2006 ; Vol. 100, No. 1. pp. 307-317.
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