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J Cereb Blood Flow Metab. 2017 Jun;37(6):2112-2124. doi: 10.1177/0271678X16661202. Epub 2016 Jan 1.

Glymphatic clearance controls state-dependent changes in brain lactate concentration.

Author information

1
1 Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester, Rochester, NY, USA.
2
2 Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK.
3
3 Center for Basic and Translational Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

KEYWORDS:

Metabolism; astrocytes; cerebrospinal fluid; glymphatic system; lactate; stroke

PMID:
27481936
PMCID:
PMC5464705
DOI:
10.1177/0271678X16661202
[Indexed for MEDLINE]
Free PMC Article

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