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

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Nicholas B BèchetIben Lundgaard

Abstract

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.

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Citations

Jan 20, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tekla Maria KylkilahtiIben Lundgaard
Mar 2, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nicholas Burdon BèchetIben Lundgaard
Apr 6, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yeerfan JiaerkenMinming Zhang
Jul 22, 2021·BMC Veterinary Research·Nagesh C ShanbhagIben Lundgaard
Oct 2, 2021·Clinical and Experimental Immunology·Luciano Stürmer de FragaVictorio Bambini-Junior
Nov 23, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yuanjian FangJohn H Zhang
Jan 1, 2022·CNS Neuroscience & Therapeutics·Hongyu LiuLing Chen

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Methods Mentioned

BETA
fluorescence microscopy
light sheet microscopy
light sheet
light microscopy
light-sheet

Software Mentioned

Arivis Vision
Fiji
Imaris

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