Is the spontaneously hypertensive stroke prone rat a pertinent model of sub cortical ischemic stroke? A systematic review
Emma L. Bailey,
Colin Smith,
Cathie L. M. Sudlow,
Joanna M. Wardlaw,
Emma L. Bailey
Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
Search for more papers by this authorColin Smith
Division of Pathology, University of Edinburgh, Edinburgh, UK
Search for more papers by this authorCathie L. M. Sudlow
Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Search for more papers by this authorCorresponding Author
Joanna M. Wardlaw
Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
SINAPSE Collaboration (Scottish Imaging Network, A Platform for Scientific Excellence), University of Edinburgh, 1 George Square, UK
Joanna M. Wardlaw*, Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU Edinburgh, UK.E-mail: [email protected]Search for more papers by this authorEmma L. Bailey,
Colin Smith,
Cathie L. M. Sudlow,
Joanna M. Wardlaw,
Emma L. Bailey
Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
Search for more papers by this authorColin Smith
Division of Pathology, University of Edinburgh, Edinburgh, UK
Search for more papers by this authorCathie L. M. Sudlow
Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Search for more papers by this authorCorresponding Author
Joanna M. Wardlaw
Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
SINAPSE Collaboration (Scottish Imaging Network, A Platform for Scientific Excellence), University of Edinburgh, 1 George Square, UK
Joanna M. Wardlaw*, Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU Edinburgh, UK.E-mail: [email protected]Search for more papers by this authorConflict of interest: None declared.
Funding: E. L. B. is funded by a Medical Research Council PhD studentship. J. M. W. is funded by the Scottish Funding Council through the SINAPSE Collaboration (Scottish Imaging Network, A Platform for Scientific Excellence, http://www.sinapse.ac.uk). C. L. M. S. is funded by the Scottish Funding Council.
Abstract
The spontaneously hypertensive stroke prone rat is best known as an inducible model of large artery stroke. Spontaneous strokes and stroke propensity in the spontaneously hypertensive stroke prone rat are less well characterized; however, could be relevant to human lacunar stroke. We systematically reviewed the literature to assess the brain tissue and small vessel pathology underlying the spontaneous strokes of the spontaneously hypertensive stroke prone rat. We searched systematically three online databases from 1970 to May 2010; excluded duplicates, reviews, and articles describing the consequences of induced middle cerebral artery occlusion or noncerebral pathology; and recorded data describing brain region and the vessels examined, number of animals, age, dietary salt intake, vascular and tissue abnormalities. Among 102 relevant studies, animals sacrificed after developing stroke-like symptoms displayed arteriolar wall thickening, subcortical lesions, enlarged perivascular spaces and cortical infarcts and hemorrhages. Histopathology, proteomics and imaging studies suggested that the changes not due simply to hypertension. There may be susceptibility to endothelial permeability increase that precedes arteriolar wall thickening, degeneration and perivascular tissue changes; systemic inflammation may also precede cerebrovascular changes. There were very few data on venules or tissue changes before hypertension. The spontaneously hypertensive stroke prone rat shows similar features to human lacunar stroke and may be a good spontaneous model of this complex human disorder. Further studies should focus on structural changes at early ages and genetics to identify factors that predispose to vascular and brain damage.
Supporting Information
Table S1. Summary of the studies included for analysis in chronological order top to bottom. Abbreviations: n/a=information unobtainable, unclear or irrelevant. BG=basal ganglia, BA=basilar artery, MCA=middle cerebral artery, ACA=anterior cerebral artery, PCA=posterior cerebral artery, CC=corpus callosum, AC=anterior commisure, IC=internal capsule, CP=caudate and putamen, GP=globus pallidus, WM=white matter, CB=cerebellum, MB=midbrain, HT=hypothalamus, MO=medulla oblongata, HP=hippocampus, ST=striatum. N=total number of experimental animals used – in general this equated to 50% WKY and 50% SHRSP unless otherwise stated. $=All SHRSP, #=SHR included as well as WKY. SHR, spontaneously hypertensive rat; SHRSP, spontaneously hypertensive stroke prone rat; WKY, Wistar Kyoto rats.
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