Morphometry of the hippocampal microvasculature in post-stroke and age-related dementias

Background Optimal vascular function is vital for prevention of dementia. We hypothesized that elderly post‐stroke survivors who preserve cognitive function show unperturbed cerebral microvasculature compared with those who develop dementia. Methods Using stereological spherical probe software, we c...

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Published inNeuropathology and applied neurobiology Vol. 40; no. 3; pp. 284 - 295
Main Authors Burke, M. J. C., Nelson, L., Slade, J. Y., Oakley, A. E., Khundakar, A. A., Kalaria, R. N.
Format Journal Article
LanguageEnglish
Published England Blackwell Publishing Ltd 01.04.2014
Wiley Subscription Services, Inc
BlackWell Publishing Ltd
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Summary:Background Optimal vascular function is vital for prevention of dementia. We hypothesized that elderly post‐stroke survivors who preserve cognitive function show unperturbed cerebral microvasculature compared with those who develop dementia. Methods Using stereological spherical probe software, we compared the length density (Lv, cumulative vessel length per unit tissue volume) of hippocampal microvessels in post mortem brain tissue from post‐stroke survivors, Alzheimer's disease (AD), vascular dementia (VaD) and normal ageing control subjects. We also assessed microvessel diameters in the same subjects. Microvessels were identified by markers of endothelial cells (glucose transporter 1; GLUT1), basement membrane (collagen IV; COL4) and smooth muscle cell α‐actin (SMA). Results We found increased Lv of both GLUT1 and COL4 immunostained microvessels (P < 0.05) in the hippocampal CA1 region of post‐stroke demented (PSD) and AD cases compared with post‐stroke nondemented (PSND), control and VaD subjects. However, no changes were apparent in the CA2 region. We also noted significant increase in Lv in the entorhinal cortex of AD compared with PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared with PSND, as well as in AD and VaD compared with controls. Cumulative frequency analysis showed PSND subjects to have significantly greater proportion of microvessels with diameters, ranging from 7 to 12 μm. Conclusions An increase in microvascular Lv in AD and PSD suggests either an increase in angiogenesis or the formation of newer microvessel loops in response to cerebral hypoperfusion. The decreased vessel diameters found in AD and VaD suggests increased vasoconstriction in dementia.
Bibliography:istex:AAAB7A5A6E8B22B35D983FB74DF6FED1D11D74F4
ark:/67375/WNG-TS6K46VH-K
Additional Supporting Information may be found in the online version of this article at the publisher's web-site: Table S1. The relationship of Lv with the burden of neuropathology.
Alzheimer's Research UK (UK)
Alzheimer's Society and Alzheimer's Research UK (ARUK)
Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases
ARUK
Newcastle Centre for Brain Ageing and Vitality (BBSRC, EPSRC, ESRC and MRC, LLHW)
ArticleID:NAN12085
UK Medical Research Council (MRC - No. G0500247; No. G0400074
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0305-1846
1365-2990
DOI:10.1111/nan.12085