Mechanisms to explain the reverse perivascular transport of solutes out of the brain
Schley, D., Carare-Nnadi, R., Please, C.P., Perry, V.H. and Weller, R.O. (2006) Mechanisms to explain the reverse perivascular transport of solutes out of the brain. Journal of Theoretical Biology, 238, (4), 962-974. (doi:10.1016/j.jtbi.2005.07.005).
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Experimental studies and observations in the human brain indicate that interstitial fluid and solutes, such as amyloid-β (Aβ), are eliminated from grey matter of the brain along pericapillary and periarterial pathways. It is unclear, however, what constitutes the motive force for such transport within blood vessel walls, which is in the opposite direction to blood flow. In this paper the potential for global pressure differences to achieve such transport are considered. A mathematical model is constructed in order to test the hypothesis that perivascular drainage of interstitial fluid and solutes out of brain tissue is driven by pulsations of the blood vessel walls. Here it is assumed that drainage occurs through a thin layer between astrocytes and endothelial cells or between smooth muscle cells. The model suggests that, during each pulse cycle, there are periods when fluid and solutes are driven along perivascular spaces in the reverse direction to the flow of blood. It is shown that successful drainage may depend upon some attachment of solutes to the lining of the perivascular space, in order to produce a valve-like effect, although an alternative without this requirement is also postulated. Reduction in pulse amplitude, as in ageing cerebral vessels, would prolong the attachment time, encourage precipitation of Aβ peptides in vessel walls, and impair elimination of Aβ from the brain. These factors may play a role in the pathogenesis of cerebral amyloid angiopathy and in the accumulation of Aβ in the brain in Alzheimer's disease.
|Keywords:||perivascular transport, thin-film flow, cerebral amyloid angiopathy, alzheimer's disease|
|Subjects:||Q Science > QA Mathematics
R Medicine > RC Internal medicine
Q Science > QH Natural history > QH301 Biology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
University Structure - Pre August 2011 > School of Biological Sciences
University Structure - Pre August 2011 > School of Medicine > Medical Education
|Date Deposited:||02 Oct 2008|
|Last Modified:||01 Jun 2011 00:36|
|Contributors:||Schley, D. (Author)
Carare-Nnadi, R. (Author)
Please, C.P. (Author)
Perry, V.H. (Author)
Weller, R.O. (Author)
|Date:||21 February 2006|
|Contact Email Address:||R.Carare-Nnadi@soton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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