Astrocyte contributions to flow/pressure-evoked parenchymal arteriole vasoconstriction

Ki Jung Kim, Jennifer A. Iddings, Javier Eduardo Stern, Víctor M. Blanco, Deborah Croom, Sergei A Kirov, Jessica Andrea Filosa

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Basal and activity-dependent cerebral blood flow changes are coordinated by the action of critical processes, including cerebral autoregulation, endothelial-mediated signaling, and neurovascular coupling. The goal of our study was to determine whether astrocytes contribute to the regulation of parenchymal arteriole (PA) tone in response to hemodynamic stimuli (pressure/flow). Cortical PA vascular responses and astrocytic Ca 2+ dynamics were measured using an in vitro rat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented with in vivo astrocytic Ca 2+ imaging. In vitro, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca 2+. Astrocytic Ca 2+ responses were corroborated in vivo, where acute systemic phenylephrine-induced increases in blood pressure evoked a significant increase in astrocytic Ca 2+. In vitro, flow/pressure-evoked vasoconstriction was blunted when the astrocytic syncytium was loaded with BAPTA (chelating intracellular Ca 2+) and enhanced when high Ca 2+ or ATP were introduced to the astrocytic syncytium. Bath application of either the TRPV4 channel blocker HC067047 or purinergic receptor antagonist suramin blunted flow/pressure-evoked vasoconstriction, whereas K + and 20-HETE signaling blockade showed no effect. Importantly, we found TRPV4 channel expression to be restricted to astrocytes and not the endothelium of PA. We present evidence for a novel role of astrocytes in PA flow/pressure-evoked vasoconstriction. Our data suggest that astrocytic TRPV4 channels are key molecular sensors of hemodynamic stimuli and that a purinergic, glial-derived signal contributes to flow/pressure-induced adjustments in PA tone. Together our results support bidirectional signaling within the neurovascular unit and astrocytes as key modulators of PA tone.

Original languageEnglish (US)
Pages (from-to)8245-8257
Number of pages13
JournalJournal of Neuroscience
Volume35
Issue number21
DOIs
StatePublished - May 27 2015

Fingerprint

Arterioles
Vasoconstriction
Astrocytes
Pressure
Giant Cells
Cerebrovascular Circulation
Purinergic Antagonists
Hemodynamics
Suramin
Phenylephrine
Baths
Neuroglia
Endothelium
Blood Vessels
Homeostasis
Adenosine Triphosphate
Blood Pressure
Brain
In Vitro Techniques

Keywords

  • Astrocyte
  • Calcium
  • Myogenic
  • Neurovascular
  • Parenchymal arteriole
  • Vascular tone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Astrocyte contributions to flow/pressure-evoked parenchymal arteriole vasoconstriction. / Kim, Ki Jung; Iddings, Jennifer A.; Stern, Javier Eduardo; Blanco, Víctor M.; Croom, Deborah; Kirov, Sergei A; Filosa, Jessica Andrea.

In: Journal of Neuroscience, Vol. 35, No. 21, 27.05.2015, p. 8245-8257.

Research output: Contribution to journalArticle

Kim, Ki Jung ; Iddings, Jennifer A. ; Stern, Javier Eduardo ; Blanco, Víctor M. ; Croom, Deborah ; Kirov, Sergei A ; Filosa, Jessica Andrea. / Astrocyte contributions to flow/pressure-evoked parenchymal arteriole vasoconstriction. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 21. pp. 8245-8257.
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AU - Kim, Ki Jung

AU - Iddings, Jennifer A.

AU - Stern, Javier Eduardo

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AU - Croom, Deborah

AU - Kirov, Sergei A

AU - Filosa, Jessica Andrea

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