Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow

Nephtali Marina; Isabel N. Christie; Alla Korsak; Maxim Doronin; Alexey Brazhe; Patrick S. Hosford; Jack A. Wells; Shahriar Sheikhbahaei; Ibrahim Humoud; Julian F.R. Paton; Mark F. Lythgoe; Alexey Semyanov; Sergey Kasparov; Alexander V. Gourine

doi:10.1038/s41467-019-13956-y

Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow

Nephtali Marina^*, Isabel N. Christie, Alla Korsak, Maxim Doronin, Alexey Brazhe, Patrick S. Hosford, Jack A. Wells, Shahriar Sheikhbahaei, Ibrahim Humoud, Julian F.R. Paton, Mark F. Lythgoe, Alexey Semyanov, Sergey Kasparov, Alexander V. Gourine

^*Corresponding author for this work

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Abstract

Astrocytes provide neurons with essential metabolic and structural support, modulate neuronal circuit activity and may also function as versatile surveyors of brain milieu, tuned to sense conditions of potential metabolic insufficiency. Here we show that astrocytes detect falling cerebral perfusion pressure and activate CNS autonomic sympathetic control circuits to increase systemic arterial blood pressure and heart rate with the purpose of maintaining brain blood flow and oxygen delivery. Studies conducted in experimental animals (laboratory rats) show that astrocytes respond to acute decreases in brain perfusion with elevations in intracellular [Ca²⁺]. Blockade of Ca²⁺-dependent signaling mechanisms in populations of astrocytes that reside alongside CNS sympathetic control circuits prevents compensatory increases in sympathetic nerve activity, heart rate and arterial blood pressure induced by reductions in cerebral perfusion. These data suggest that astrocytes function as intracranial baroreceptors and play an important role in homeostatic control of arterial blood pressure and brain blood flow.

Original language	English
Article number	131 (2020)
Number of pages	9
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13956-y
Publication status	Published - 9 Jan 2020

Keywords

arterial blood pressure
astrocytes
brain blood flow
cardiac output
heart rate
sympathetic

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Marina, N., Christie, I. N., Korsak, A., Doronin, M., Brazhe, A., Hosford, P. S., Wells, J. A., Sheikhbahaei, S., Humoud, I., Paton, J. F. R., Lythgoe, M. F., Semyanov, A., Kasparov, S., & Gourine, A. V. (2020). Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow. Nature Communications, 11(1), Article 131 (2020). https://doi.org/10.1038/s41467-019-13956-y

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Marina, N, Christie, IN, Korsak, A, Doronin, M, Brazhe, A, Hosford, PS, Wells, JA, Sheikhbahaei, S, Humoud, I, Paton, JFR, Lythgoe, MF, Semyanov, A, Kasparov, S & Gourine, AV 2020, 'Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow', Nature Communications, vol. 11, no. 1, 131 (2020). https://doi.org/10.1038/s41467-019-13956-y

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AU - Brazhe, Alexey

AU - Hosford, Patrick S.

AU - Wells, Jack A.

AU - Sheikhbahaei, Shahriar

AU - Humoud, Ibrahim

AU - Paton, Julian F.R.

AU - Lythgoe, Mark F.

AU - Semyanov, Alexey

AU - Kasparov, Sergey

AU - Gourine, Alexander V.

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AB - Astrocytes provide neurons with essential metabolic and structural support, modulate neuronal circuit activity and may also function as versatile surveyors of brain milieu, tuned to sense conditions of potential metabolic insufficiency. Here we show that astrocytes detect falling cerebral perfusion pressure and activate CNS autonomic sympathetic control circuits to increase systemic arterial blood pressure and heart rate with the purpose of maintaining brain blood flow and oxygen delivery. Studies conducted in experimental animals (laboratory rats) show that astrocytes respond to acute decreases in brain perfusion with elevations in intracellular [Ca2+]. Blockade of Ca2+-dependent signaling mechanisms in populations of astrocytes that reside alongside CNS sympathetic control circuits prevents compensatory increases in sympathetic nerve activity, heart rate and arterial blood pressure induced by reductions in cerebral perfusion. These data suggest that astrocytes function as intracranial baroreceptors and play an important role in homeostatic control of arterial blood pressure and brain blood flow.

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Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow

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