Light sheet fluorescence microscopy of optically cleared brains for studying the glymphatic system

Nicholas B. Bèchet, Tekla M. Kylkilahti, Bengt Mattsson, Martina Petrasova, Nagesh C. Shanbhag, Iben Lundgaard

Research output: Contribution to journalArticlepeer-review


Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer’s disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awake state and by other anaesthetics. Here we investigated whether light sheet fluorescence microscopy of whole optically cleared murine brains was capable of detecting glymphatic differences in sleep- and awake-mimicking anaesthesia, respectively. Using light-sheet imaging of whole brains, we found anaesthetic-dependent cerebrospinal fluid (CSF) influx differences, including reduced tracer influx along tertiary branches of the middle cerebral artery and reduced influx along dorsal and anterior penetrating arterioles, in the awake-mimicking anaesthesia. This study establishes that light sheet microscopy of optically cleared brains is feasible for quantitative analyses and can provide images of the entire glymphatic system in whole brains.

Original languageEnglish
Pages (from-to)1975-1986
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number10
Early online date2020
Publication statusPublished - 2020 Oct 1

Subject classification (UKÄ)

  • Other Medical Engineering
  • Neurology

Free keywords

  • anaesthesia
  • cerebrospinal fluid
  • Glymphatic system
  • light sheet microscopy
  • optical tissue clearing


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