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- W1965383205 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<sup>2+</sup> dynamics were measured using an <i>in vitro</i> rat/mouse brain slice model of perfused/pressurized PAs; studies were supplemented with <i>in vivo</i> astrocytic Ca<sup>2+</sup> imaging. <i>In vitro</i>, astrocytes responded to PA flow/pressure increases with an increase in intracellular Ca<sup>2+</sup>. Astrocytic Ca<sup>2+</sup> responses were corroborated <i>in vivo</i>, where acute systemic phenylephrine-induced increases in blood pressure evoked a significant increase in astrocytic Ca<sup>2+</sup>. <i>In vitro</i>, flow/pressure-evoked vasoconstriction was blunted when the astrocytic syncytium was loaded with BAPTA (chelating intracellular Ca<sup>2+</sup>) and enhanced when high Ca<sup>2+</sup> 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<sup>+</sup> 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." @default.
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- W1965383205 date "2010-09-01" @default.
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- W1965383205 title "Mixed treatment comparisons to evaluate the effectiveness of strategies for preventing fire related injuries in children within the home" @default.
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- W1965383205 doi "https://doi.org/10.1136/ip.2010.029215.758" @default.
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