Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain.

Ma, Qiaoli; Ries, Miriam; Decker, Yann; Müller, Andreas; Riner, Chantal; Bücker, Arno; Fassbender, Klaus; Detmar, Michael; Proulx, Steven T. (2019). Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain. Acta neuropathologica, 137(1), pp. 151-165. Springer-Verlag 10.1007/s00401-018-1916-x

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The relationships between cerebrospinal fluid (CSF) and brain interstitial fluid are still being elucidated. It has been proposed that CSF within the subarachnoid space will enter paravascular spaces along arteries to flush through the parenchyma of the brain. However, CSF also directly exits the subarachnoid space through the cribriform plate and other perineural routes to reach the lymphatic system. In this study, we aimed to elucidate the functional relationship between CSF efflux through lymphatics and the potential influx into the brain by assessment of the distribution of CSF-infused tracers in awake and anesthetized mice. Using near-infrared fluorescence imaging, we showed that tracers quickly exited the subarachnoid space by transport through the lymphatic system to the systemic circulation in awake mice, significantly limiting their spread to the paravascular spaces of the brain. Magnetic resonance imaging and fluorescence microscopy through the skull under anesthetized conditions indicated that tracers remained confined to paravascular spaces on the surface of the brain. Immediately after death, a substantial influx of tracers occurred along paravascular spaces extending into the brain parenchyma. We conclude that under normal conditions a rapid CSF turnover through lymphatics precludes significant bulk flow into the brain.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0001-6322

Publisher:

Springer-Verlag

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

13 Nov 2019 15:40

Last Modified:

05 Dec 2022 15:32

Publisher DOI:

10.1007/s00401-018-1916-x

PubMed ID:

30306266

Uncontrolled Keywords:

Anesthesia Cerebrospinal fluid Lymphatic vessel Paravascular space

BORIS DOI:

10.7892/boris.134713

URI:

https://boris.unibe.ch/id/eprint/134713

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