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

Bèchet, Nicholas B. LU ; Kylkilahti, Tekla M. LU ; Mattsson, Bengt LU ; Petrasova, Martina ; Shanbhag, Nagesh C. LU and Lundgaard, Iben LU (2020) In Journal of Cerebral Blood Flow and Metabolism 40(10). p.1975-1986
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)... (More)

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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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
anaesthesia, cerebrospinal fluid, Glymphatic system, light sheet microscopy, optical tissue clearing
in
Journal of Cerebral Blood Flow and Metabolism
volume
40
issue
10
pages
12 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:32525440
  • scopus:85086339377
ISSN
0271-678X
DOI
10.1177/0271678X20924954
language
English
LU publication?
yes
id
2e1f7698-bdad-4968-9fc5-f45d5acc8896
date added to LUP
2020-07-10 13:45:12
date last changed
2024-10-17 06:58:40
@article{2e1f7698-bdad-4968-9fc5-f45d5acc8896,
  abstract     = {{<p>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.</p>}},
  author       = {{Bèchet, Nicholas B. and Kylkilahti, Tekla M. and Mattsson, Bengt and Petrasova, Martina and Shanbhag, Nagesh C. and Lundgaard, Iben}},
  issn         = {{0271-678X}},
  keywords     = {{anaesthesia; cerebrospinal fluid; Glymphatic system; light sheet microscopy; optical tissue clearing}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{10}},
  pages        = {{1975--1986}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Journal of Cerebral Blood Flow and Metabolism}},
  title        = {{Light sheet fluorescence microscopy of optically cleared brains for studying the glymphatic system}},
  url          = {{http://dx.doi.org/10.1177/0271678X20924954}},
  doi          = {{10.1177/0271678X20924954}},
  volume       = {{40}},
  year         = {{2020}},
}