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


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, p.223. (doi:10.1111/j.1365-2990.2006.00749.x).

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Description/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-β 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 μm 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 μm 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-β in CAA and of
fluid around arteries in the white matter in Alzheimer’s
disease.

Item Type: Article
ISSNs: 0305-1846 (print)
Related URLs:
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 55926
Date Deposited: 06 Aug 2008
Last Modified: 27 Mar 2014 18:38
URI: http://eprints.soton.ac.uk/id/eprint/55926

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