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Fluids Barriers CNS. 2015 Oct 5;12:23. doi: 10.1186/s12987-015-0019-5.

Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system.

Author information

1
Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. b.bedussi@amc.uva.nl.
2
Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. m.g.vanlier@amc.uva.nl.
3
Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. jbartstra@hotmail.com.
4
Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. j.devos@amc.uva.nl.
5
Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. m.siebes@amc.uva.nl.
6
Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. e.vanbavel@amc.uva.nl.
7
Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. n.t.bakker@amc.uva.nl.

Abstract

BACKGROUND:

In the absence of a true lymphatic system in the brain parenchyma, alternative clearance pathways for excess fluid and waste products have been proposed. Suggested mechanisms for clearance implicate a role for brain interstitial and cerebrospinal fluids. However, the proposed direction of flow, the anatomical structures involved, and the driving forces are controversial.

METHODS:

To trace the distribution of interstitial and cerebrospinal fluid in the brain, and to identify the anatomical structures involved, we infused a mix of fluorescent tracers with different sizes into the cisterna magna or striatum of mouse brains. We subsequently performed confocal fluorescence imaging of horizontal brain sections and made 3D reconstructions of the mouse brain and vasculature.

RESULTS:

We observed a distribution pattern of tracers from the parenchyma to the ventricular system, from where tracers mixed with the cerebrospinal fluid, reached the subarachnoid space, and left the brain via the cribriform plate and the nose. Tracers also entered paravascular spaces around arteries both after injection in the cisterna magna and striatum, but this appeared to be of minor importance.

CONCLUSION:

These data suggest a bulk flow of interstitial fluid from the striatum towards the adjacent lateral ventricle. Tracers may enter arterial paravascular spaces from two sides, both through bulk flow from the parenchyma and through mixing of CSF in the subarachnoid space. Disturbances in this transport pathway could influence the drainage of amyloid β and other waste products, which may be relevant for the pathophysiology of Alzheimer's disease.

PMID:
26435380
PMCID:
PMC4593194
DOI:
10.1186/s12987-015-0019-5
[Indexed for MEDLINE]
Free PMC Article

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