Sci. STKE, 7 February 2006
BRAIN A Fresh View on Astrocyte Regulation of Blood Flow
Neural activity leads to a localized increase in blood flow to accommodate the increased metabolic demand. Although astrocytes (whose endfeet appose cerebral blood vessels) have long been suspected of playing a leading role in this functional hyperemia, exactly what they do and how they do it has been controversial (see Rossi). Takano et al. used calcium imaging and photolysis of caged calcium to investigate the role of astrocytes in regulating local microcirculation in the somatosensory cortex of anesthetized adult mice. After confirming that the calcium indicator Rhod-2 was preferentially taken up by astrocytes, the authors loaded Rhod-2 and caged calcium into astrocytes and visualized the vasculature with fluorescein-5-isothiocyanate-conjugated dextran (FITC-dextran). Localized photolysis of caged calcium in the endfeet of astrocytes in contact with arteries led to an increase in endfoot calcium concentration (which sometimes propagated back to the astrocyte body) associated with rapid vasodilatation (measured as an increase in arterial cross-sectional area). Pharmacological analysis indicated that this vasodilatation primarily involved phospholipase A2 (PLA2)-dependent generation of arachidonic acid and its subsequent metabolism by cyclooxygenase 1 (COX1). Electrical stimulation (to elicit local increases in neural activity) also stimulated an increase in astrocyte calcium concentration and vasodilatation, as well as increasing blood flow. Pharmacological analysis indicated that this activity-mediated hyperemia depended in part on the activation of mGluR5 metabotropic glutamate receptors (which are found on astrocytes) and the PLA2-COX1 pathway. Thus, the authors conclude that astrocytes contribute to local vasodilatation in response to neural activity through a pathway involving the calcium- and PLA2-dependent release of COX1 metabolites.
T. Takano, G.-F. Tian, W. Peng, N. Lou, W. Libionka, X. Han, M. Nedergaard, Astrocyte-mediated control of cerebral blood flow. Nat. Neurosci. 9, 260-267 (2006). [PubMed]
D. J. Rossi, Another BOLD role for astrocytes: Coupling blood flow to neural activity. Nat. Neurosci. 9, 159-161 (2006). [PubMed]
Citation: A Fresh View on Astrocyte Regulation of Blood Flow. Sci. STKE 2006, tw49 (2006).
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