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

NB. Bèchet, TM. Kylkilahti, B. Mattsson, M. Petrasova, NC. Shanbhag, I. Lundgaard

. 2020 ; 40 (10) : 1975-1986. [pub] 20200611

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

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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$a Kylkilahti, Tekla M $u Department of Experimental Medical Science, Lund University, Lund, Sweden ; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden
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$a Mattsson, Bengt $u Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden
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$a Petrasova, Martina $u Department of Experimental Medical Science, Lund University, Lund, Sweden ; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden ; Department of Neurology, University Hospital Brno, Brno, Czech Republic
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$a Shanbhag, Nagesh C $u Department of Experimental Medical Science, Lund University, Lund, Sweden ; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden
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