Details

Autor(en) / Beteiligte

• MacVicar, Brian A
• Gordon, Grant R. J
• Choi, Hyun B
• Rungta, Ravi L
• Ellis-Davies, Graham C. R

Titel

Brain metabolism dictates the polarity of astrocyte control over arterioles

Ist Teil von

• Nature, 2008-12, Vol.456 (7223), p.745-749

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2008

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E 2 , leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation. A rush of blood to the head? Cerebral blood flow is tightly coupled to neuronal activity, a relationship that is fundamental to functional imaging techniques such as MRI. Calcium signalling in glial cells (specifically astrocytes) is known to couple neuronal activity to regional changes in cerebral blood flow, but what determines the polarity of its effect on the arterioles — vasoconstricting versus vasodilating — remains in doubt. A new study shows that the balance between these two effects depends on brain metabolism. When the glycolytic state of the brain is enhanced by lower tissue oxygenation, astrocyte-mediated vasoconstrictions convert to vasodilations. Manipulating this homeo-static balance may be of therapeutic value for treating declines in blood supply to the brain that occur in some dementias or after a stroke. Calcium signalling in glial cells couples neuronal activity to regional changes in cerebral blood flow, but the polarity of its effect on the diameter of neighbouring arterioles has remained controversial. This paper reveals that when the glycolytic state of the brain is enhanced by lower tissue oxygenation, glia-mediated vasoconstrictions convert to vasodilations.