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Lookup NU author(s): Matthew Burke, Lucy Nelson, Janet Slade, Arthur Oakley, Dr Ahmad Khundakar, Professor Raj KalariaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
BACKGROUND: Optimal vascular function is vital for prevention of dementia. We hypothesised that elderly post-stroke (PS) survivors who preserve cognitive function show unperturbed cerebral microvasculature compared to 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 PS 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 to post-stroke non-demented (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 to PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared to PSND, as well as in AD and VaD compared to 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.
Author(s): Burke MJC, Nelson L, Slade JY, Oakley AE, Khundakar AA, Kalaria RN
Publication type: Article
Publication status: Published
Journal: Neuropathology and Applied Neurobiology
Year: 2014
Volume: 40
Issue: 3
Pages: 284-295
Print publication date: 01/04/2014
Online publication date: 13/03/2014
Acceptance date: 29/08/2013
Date deposited: 24/03/2014
ISSN (print): 0305-1846
ISSN (electronic): 1365-2990
Publisher: Wiley-Blackwell
URL: http://dx.doi.org/10.1111/nan.12085
DOI: 10.1111/nan.12085
PubMed id: 24003901
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