Glymphatic clearance controls state-dependent changes in brain lactate concentration

Iben Lundgaard, Minh Lon Lu, Ezra Yang, Weiguo Peng, Humberto Mestre, Emi Hitomi, Rashid Deane, Maiken Nedergaard

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2112-2124
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number6
Publication statusPublished - 2017 Jun 1
Externally publishedYes

Subject classification (UKÄ)

  • Neurosciences

Free keywords

  • Astrocytes
  • Cerebrospinal fluid
  • Glymphatic system
  • Lactate
  • Metabolism
  • Stroke


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