Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats

Bailey, E.L. , Wardlaw, J.M., Graham, D. , Dominiczak, A.F. , Sudlow, C.L.M. and Smith, C. (2011) Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats. Neuropathology and Applied Neurobiology, 37(7), pp. 711-726. (doi:10.1111/j.1365-2990.2011.01170.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2990.2011.01170.x

Abstract

<p><b>Aims:</b> The spontaneously hypertensive stroke-prone rat (SHRSP) is a potential animal model of human lacunar stroke, but there is little information on SHRSP small vessel pathology, especially in young rats. We investigated the structural changes that occur in cortical and subcortical vessels and adjacent tissue in SHRSP before, during and after the onset of hypertension.</p> <p><b>Methods:</b> We examined brains from SHRSP and Wistar Kyoto rats (WKY) at 5, 16 and 21 weeks of age. Structural changes in small arterioles and adjacent tissue were studied using antibodies to investigate different components of the neurovascular unit. We quantified staining in three standard regions, at two coronal levels.</p> <p><b>Results:</b> Immunostaining for claudin-5, a marker of endothelial tight junctions, was reduced in SHRSP at all ages compared to age-matched WKY controls. Smooth muscle actin, glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 were increased in SHRSP vs. WKY by 16 weeks. Additionally, 21-week-old WKY and SHRSP rats fed a high-salt diet showed differences in claudin-5, glial fibrillary acidic protein and matrix metalloproteinase 9 staining compared to those fed a normal diet.</p> <p><b>Conclusion:</b> Endothelial tight junction alterations of SHRSP rats from the earliest ages point towards increased susceptibility to blood-brain barrier dysfunction and stroke, which is exacerbated by salt loading. Salt loading may also damage the neurovascular unit in WKY controls.</p>

Item Type:Articles
Keywords:Blood–brain barrier, immunohistochistry, salt loading, SHRSP, small vessel disease
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bailey, Dr Emma and Dominiczak, Professor Anna and Graham, Dr Delyth
Authors: Bailey, E.L., Wardlaw, J.M., Graham, D., Dominiczak, A.F., Sudlow, C.L.M., and Smith, C.
Subjects:R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Neuropathology and Applied Neurobiology
Publisher:Blackwell
ISSN:0305-1846
Published Online:27 October 2011

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