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Connections between perivascular interstitial fluid drainage pathways in the brain: Significance for Alzheimer's disease and neuroimmunology

Connections between perivascular interstitial fluid drainage pathways in the brain: Significance for Alzheimer's disease and neuroimmunology
Connections between perivascular interstitial fluid drainage pathways in the brain: Significance for Alzheimer's disease and neuroimmunology
Introduction: Solutes injected into the interstitial fluid (ISF) of mouse brains drain along basement membranes of capillaries and arteries in a pattern that closely resembles the deposition of amyloid-? in cerebral amyloid angiopathy (CAA). Injected particles (fluorospheres) expand peripheral perivascular spaces in a similar way to the dilatation of perivascular spaces by fluid in the cerebral white matter in Alzheimer’s disease. Here, we test the hypothesis that the drainage route for ISF in vascular basement membranes connects with drainage pathways at the periphery of arteries.
Materials and methods: Soluble dextran or 0.02 ?m fluorospheres were injected into brains of 109 mice; animals were fixed by perfusion at intervals up to 1 week. The effect of inflammation was tested by co-injection of the tracers with LPS or kainic acid. The distribution of tracers was characterized using immunofluorescence, image analysis and confocal microscopy.
Results: Soluble dextran spread progressively along capillary and artery basement membranes over 3–24 h to leptomeningeal arteries and radially through arterial walls to be taken up by perivascular cells. No spread occurred when tracer was injected into dead animals. Following injection, 0.02 ?m fluorospheres expanded spaces at the periphery of arteries and capillaries and were ingested by perivascular cells. Co-injection with LPS or kainic acid resulted in wider distribution of soluble and particulate tracers.
Conclusions: These results suggest that antigens draining in ISF along vascular basement membranes may enter pathways at the periphery of arteries and be sampled by perivascular cells. This interconnection may also help to explain the distribution of amyloid-? in CAA and of fluid around arteries in the white matter in Alzheimer’s disease.
0305-1846
p.223
Carare-Nnadi, R.
542a95ac-8764-4edb-82a8-63bc38bb533c
Bernardes-Silva, M.
513d0bcc-f15d-44d6-9373-a0d78b2b2e07
Subash, M.
7c507d5f-2ef4-4ce9-bb75-8a128021ce9d
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Weller, R.O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare-Nnadi, R.
542a95ac-8764-4edb-82a8-63bc38bb533c
Bernardes-Silva, M.
513d0bcc-f15d-44d6-9373-a0d78b2b2e07
Subash, M.
7c507d5f-2ef4-4ce9-bb75-8a128021ce9d
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Weller, R.O.
4a501831-e38a-4d39-a125-d7141d6c667b

Carare-Nnadi, R., Bernardes-Silva, M., Subash, M., Perry, V.H. and Weller, R.O. (2006) Connections between perivascular interstitial fluid drainage pathways in the brain: Significance for Alzheimer's disease and neuroimmunology. Neuropathology and Applied Neurobiology, 32 (2), p.223. (doi:10.1111/j.1365-2990.2006.00749.x).

Record type: Article

Abstract

Introduction: Solutes injected into the interstitial fluid (ISF) of mouse brains drain along basement membranes of capillaries and arteries in a pattern that closely resembles the deposition of amyloid-? in cerebral amyloid angiopathy (CAA). Injected particles (fluorospheres) expand peripheral perivascular spaces in a similar way to the dilatation of perivascular spaces by fluid in the cerebral white matter in Alzheimer’s disease. Here, we test the hypothesis that the drainage route for ISF in vascular basement membranes connects with drainage pathways at the periphery of arteries.
Materials and methods: Soluble dextran or 0.02 ?m fluorospheres were injected into brains of 109 mice; animals were fixed by perfusion at intervals up to 1 week. The effect of inflammation was tested by co-injection of the tracers with LPS or kainic acid. The distribution of tracers was characterized using immunofluorescence, image analysis and confocal microscopy.
Results: Soluble dextran spread progressively along capillary and artery basement membranes over 3–24 h to leptomeningeal arteries and radially through arterial walls to be taken up by perivascular cells. No spread occurred when tracer was injected into dead animals. Following injection, 0.02 ?m fluorospheres expanded spaces at the periphery of arteries and capillaries and were ingested by perivascular cells. Co-injection with LPS or kainic acid resulted in wider distribution of soluble and particulate tracers.
Conclusions: These results suggest that antigens draining in ISF along vascular basement membranes may enter pathways at the periphery of arteries and be sampled by perivascular cells. This interconnection may also help to explain the distribution of amyloid-? in CAA and of fluid around arteries in the white matter in Alzheimer’s disease.

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More information

e-pub ahead of print date: 13 March 2006
Published date: 1 April 2006
Additional Information: Proceedings of the 107th Meeting of the British Neuropathological Society held at the Institute of Child Health, London (p 221-249)

Identifiers

Local EPrints ID: 55926
URI: http://eprints.soton.ac.uk/id/eprint/55926
ISSN: 0305-1846
PURE UUID: 8ebf1d52-dc2f-4002-9b8f-75974caa768d

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Date deposited: 06 Aug 2008
Last modified: 15 Mar 2024 10:58

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Contributors

Author: R. Carare-Nnadi
Author: M. Bernardes-Silva
Author: M. Subash
Author: V.H. Perry
Author: R.O. Weller

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