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Immune complexes formed in the brain disrupt the perivascular drainage of solutes and interstitial fluid: significance for immunotherapy in Alzheimer's disease

Immune complexes formed in the brain disrupt the perivascular drainage of solutes and interstitial fluid: significance for immunotherapy in Alzheimer's disease
Immune complexes formed in the brain disrupt the perivascular drainage of solutes and interstitial fluid: significance for immunotherapy in Alzheimer's disease
Introduction: When 3 kDa soluble fluorescent dextran or 40 kDa ovalbumin are injected into the mouse striatum, they spread diffusely through the brain parenchyma and rapidly drain out of the brain along perivascular basement membranes surrounding capillaries and arteries. In the present study we test the hypothesis that immune complexes formed in the brain disrupt the perivascular drainage of solutes.
Material and methods: Immune complexes were formed in the brain by actively immunizing mice against ovalbumin and then injecting ovalbumin intracerebrally. Twenty-four hours later dextran tracer was injected into the brain at the same site and animals killed 5 min and 3 h later.
Results: At 5 min and 3 h after injection of the dextran tracer into the brains of immunized mice, immune complexes were located in the walls of arteries (as shown by Teeling et al. at this meeting). There was a significant reduction in the diffuse spread of dextran in the brain parenchyma and significantly fewer capillary and artery basement membranes contained dextran at 5 min when compared with the nonimmunized controls. Instead, the dextran tracer was concentrated in the perivenous spaces that were occupied by inflammatory cells.
Conclusions: The results suggest that immune complexes disrupt and alter the pattern of perivascular drainage of solutes from the brain. This may have significance for inflammatory diseases in the brain and for immunotherapy for Alzheimer’s disease in which immune complexes may form and further block the perivascular drainage pathways that is already compromised by the deposition of amyloidbeta. This work is supported by the Alzheimer Research Trust.
brain, disease, drainage, perivascular drainage of solutes, interstitial fluid, immunotherapy, alzheimer's disease
0305-1846
p.2
Carare, R.O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Teeling, J.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Weller, R.O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, R.O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Teeling, J.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Weller, R.O.
4a501831-e38a-4d39-a125-d7141d6c667b

Carare, R.O., Teeling, J., Perry, V.H., Nicoll, J.A.R. and Weller, R.O. (2008) Immune complexes formed in the brain disrupt the perivascular drainage of solutes and interstitial fluid: significance for immunotherapy in Alzheimer's disease. Neuropathology and Applied Neurobiology, 34 (Supplement 1), p.2. (doi:10.1111/j.1365-2990.2007.00921.x).

Record type: Article

Abstract

Introduction: When 3 kDa soluble fluorescent dextran or 40 kDa ovalbumin are injected into the mouse striatum, they spread diffusely through the brain parenchyma and rapidly drain out of the brain along perivascular basement membranes surrounding capillaries and arteries. In the present study we test the hypothesis that immune complexes formed in the brain disrupt the perivascular drainage of solutes.
Material and methods: Immune complexes were formed in the brain by actively immunizing mice against ovalbumin and then injecting ovalbumin intracerebrally. Twenty-four hours later dextran tracer was injected into the brain at the same site and animals killed 5 min and 3 h later.
Results: At 5 min and 3 h after injection of the dextran tracer into the brains of immunized mice, immune complexes were located in the walls of arteries (as shown by Teeling et al. at this meeting). There was a significant reduction in the diffuse spread of dextran in the brain parenchyma and significantly fewer capillary and artery basement membranes contained dextran at 5 min when compared with the nonimmunized controls. Instead, the dextran tracer was concentrated in the perivenous spaces that were occupied by inflammatory cells.
Conclusions: The results suggest that immune complexes disrupt and alter the pattern of perivascular drainage of solutes from the brain. This may have significance for inflammatory diseases in the brain and for immunotherapy for Alzheimer’s disease in which immune complexes may form and further block the perivascular drainage pathways that is already compromised by the deposition of amyloidbeta. This work is supported by the Alzheimer Research Trust.

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More information

Published date: 4 January 2008
Additional Information: Abstracts of the 109th Meeting of the British Neuropathological Society: Oral Abstracts (p 1-16)
Keywords: brain, disease, drainage, perivascular drainage of solutes, interstitial fluid, immunotherapy, alzheimer's disease

Identifiers

Local EPrints ID: 62349
URI: https://eprints.soton.ac.uk/id/eprint/62349
ISSN: 0305-1846
PURE UUID: b88c85c6-f1c5-484e-b55b-4d9d13612ec3
ORCID for J.A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

Catalogue record

Date deposited: 21 Apr 2009
Last modified: 14 Mar 2019 01:45

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