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

37 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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