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Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology

Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology
Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology
Elimination of interstitial fluid and solutes plays a role in homeostasis in the brain, but the pathways are unclear. Previous work suggests that interstitial fluid drains along the walls of arteries. Aims: to define the pathways within the walls of capillaries and arteries for drainage of fluid and solutes out of the brain. Methods: Fluorescent soluble tracers, dextran (3?kDa) and ovalbumin (40?kDa), and particulate fluospheres (0.02??m and 1.0??m in diameter) were injected into the corpus striatum of mice. Brains were examined from 5?min to 7?days by immunocytochemistry and confocal microscopy. Results: soluble tracers initially spread diffusely through brain parenchyma and then drain out of the brain along basement membranes of capillaries and arteries. Some tracer is taken up by vascular smooth muscle cells and by perivascular macrophages. No perivascular drainage was observed when dextran was injected into mouse brains following cardiac arrest. Fluospheres expand perivascular spaces between vessel walls and surrounding brain, are ingested by perivascular macrophages but do not appear to leave the brain even following an inflammatory challenge with lipopolysaccharide or kainate. Conclusions: capillary and artery basement membranes act as `lymphatics of the brain' for drainage of fluid and solutes; such drainage appears to require continued cardiac output as it ceases following cardiac arrest. This drainage pathway does not permit migration of cells from brain parenchyma to the periphery. Amyloid-? is deposited in basement membrane drainage pathways in cerebral amyloid angiopathy, and may impede elimination of amyloid-? and interstitial fluid from the brain in Alzheimer's disease. Soluble antigens, but not cells, drain from the brain by perivascular pathways. This atypical pattern of drainage may contribute to partial immune privilege of the brain and play a role in neuroimmunological diseases such as multiple sclerosis.
alzheimer's disease, brain, cerebral amyloid angiopathy, dextran, fluospheres, neuroimmunology, ovalbumin, perivascular drainage of solutes
0305-1846
131-144
Carare, R.O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Bernardes-Silva, M.
513d0bcc-f15d-44d6-9373-a0d78b2b2e07
Newman, T.A.
322290cb-2e9c-445d-a047-00b1bea39a25
Page, A.M.
50f4c392-8040-4ef5-bbd4-f285be795956
Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Weller, R.O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, R.O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Bernardes-Silva, M.
513d0bcc-f15d-44d6-9373-a0d78b2b2e07
Newman, T.A.
322290cb-2e9c-445d-a047-00b1bea39a25
Page, A.M.
50f4c392-8040-4ef5-bbd4-f285be795956
Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Weller, R.O.
4a501831-e38a-4d39-a125-d7141d6c667b

Carare, R.O., Bernardes-Silva, M., Newman, T.A., Page, A.M., Nicoll, J.A.R., Perry, V.H. and Weller, R.O. (2008) Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathology and Applied Neurobiology, 34 (2), 131-144. (doi:10.1111/j.1365-2990.2007.00926.x).

Record type: Article

Abstract

Elimination of interstitial fluid and solutes plays a role in homeostasis in the brain, but the pathways are unclear. Previous work suggests that interstitial fluid drains along the walls of arteries. Aims: to define the pathways within the walls of capillaries and arteries for drainage of fluid and solutes out of the brain. Methods: Fluorescent soluble tracers, dextran (3?kDa) and ovalbumin (40?kDa), and particulate fluospheres (0.02??m and 1.0??m in diameter) were injected into the corpus striatum of mice. Brains were examined from 5?min to 7?days by immunocytochemistry and confocal microscopy. Results: soluble tracers initially spread diffusely through brain parenchyma and then drain out of the brain along basement membranes of capillaries and arteries. Some tracer is taken up by vascular smooth muscle cells and by perivascular macrophages. No perivascular drainage was observed when dextran was injected into mouse brains following cardiac arrest. Fluospheres expand perivascular spaces between vessel walls and surrounding brain, are ingested by perivascular macrophages but do not appear to leave the brain even following an inflammatory challenge with lipopolysaccharide or kainate. Conclusions: capillary and artery basement membranes act as `lymphatics of the brain' for drainage of fluid and solutes; such drainage appears to require continued cardiac output as it ceases following cardiac arrest. This drainage pathway does not permit migration of cells from brain parenchyma to the periphery. Amyloid-? is deposited in basement membrane drainage pathways in cerebral amyloid angiopathy, and may impede elimination of amyloid-? and interstitial fluid from the brain in Alzheimer's disease. Soluble antigens, but not cells, drain from the brain by perivascular pathways. This atypical pattern of drainage may contribute to partial immune privilege of the brain and play a role in neuroimmunological diseases such as multiple sclerosis.

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More information

Published date: April 2008
Keywords: alzheimer's disease, brain, cerebral amyloid angiopathy, dextran, fluospheres, neuroimmunology, ovalbumin, perivascular drainage of solutes

Identifiers

Local EPrints ID: 55928
URI: https://eprints.soton.ac.uk/id/eprint/55928
ISSN: 0305-1846
PURE UUID: 8868e48f-131a-4ac6-8a5f-0d815051a76f
ORCID for T.A. Newman: ORCID iD orcid.org/0000-0002-3727-9258
ORCID for J.A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

Catalogue record

Date deposited: 08 Aug 2008
Last modified: 12 Nov 2019 01:59

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