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

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).

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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Contributors

Author: R.O. Carare

Author: J. Teeling

Author: J.A.R. Nicoll

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