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| Animal model | Model origin/characteristics | Systemic vascular pathology | Cerebrovascular features |
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| Spontaneously hypertensive rat (SHR) | Inbred rat obtained by crossing Wistar-Kyoto rats with high blood pressure [29, 30] | Apart from impaired endothelial reactivity, no gross vascular abnormalities, specifically no atheromatosis, vascular thrombosis, fibrinoid necrosis, or hyaline degeneration [30]. Cardiac hypertrophy and renal insufficiency with proteinuria developing at the age of 40-50 weeks | In permanent distal MCAO or photothrombosis, NogoA-neutralizing antibody increased sensorimotor recovery and contralesional corticospinal plasticity in SHR and normotensive rats [32]. Only subtle brain changes of neurotrophic factors and their receptors (BDNF, neutrophin-3/4, TrkA/TrkB) noted in SHR compared to normotensive controls [33]. Postischemic neurogenesis and oligodendrogenesis after transient proximal MCAO prematurely attenuated in middle-aged (i.e., 12-month-old) compared to young (3-month-old) SHR [34] |
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| Dahl salt-sensitive rat (DSR) | Inbred rat obtained by mating Sprague-Dawley rats exhibiting severe hypertension upon high-salt diet (8% NaCl) [37] | Fibrinoid necrosis, hyaline degeneration, and hyperplasia of arterioles and small artery walls [37]. Cardiac hypertrophy, interstitial fibrosis, and cardiac failure at ~4-5 months [37]. Glomerular sclerosis with renal insufficiency | In up to 54% of DSR on high-salt diet, fulminant spontaneous brain infarcts associated with massive aortic thickening, neurological deficits, and death noted [37]. Blood pressure, aortic thickening, stroke size, and animal mortality reduced by adenoviral kallikrein delivery [37] |
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| mRenTg mouse | Transgenic mouse overexpressing mouse renin under a liver-specific albumin promoter/enhancer [16] | Hyaline degeneration and hyperplasia of arterioles and small artery walls. Cardiac hypertrophy and proteinuria noted at 3-8 months. 50% of males died between 6 and 8 months of age | After transient proximal MCAO, infarct volume did not differ between mRenTg and wild-type mice [16]. Platelet deactivation by glycoprotein-Ib or glycoprotein-VI inhibition reduced infarct volume in mRenTg and wild-type mice without increasing brain hemorrhages [16]. Glycoprotein-IIb/IIIa inhibition did not influence infarct volume but increased brain hemorrhages more strongly in mRenTg than wild-type mice [16] |
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| hRenAngTg mouse | Transgenic mouse expressing human renin and human angiotensinogen flanked by their regulatory sequences [38, 39] | Hyaline degeneration and hyperplasia of arterioles and small artery walls | When exposed to high-salt diet and treated with an endothelial NO synthase inhibitor, spontaneous hemorrhages noted in brains of hRenAngTg mice [38]. After permanent proximal MCAO, infarct volume and neurological deficits increased in hRenAngTg mice compared to wild-type mice [39]. Effects attributed to neuronal death-promoting actions of angiotensin-II. Ex vivo, neuronal injury after oxygen-glucose deprivation more severe in slices obtained from hRenAngTg than wild-type mice [39]. Effect abolished by angiotensin type-1 receptor inhibitor lorsartan [39] |
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| Renovascular hypertensive rat | Renal hypertension induced by renal artery clipping, leaving contralateral kidney intact (“two kidneys, one clip”) or clipping both kidneys (“two kidneys, two clips”) [40, 41] | Fibrinoid necrosis, hyaline degeneration, and hyperplasia of arterioles and small artery walls associated with microaneurysms and thrombotic vascular occlusions. Cardiac hypertrophy noted in ~25-50% of rats | “Two kidneys, one clip” rats exhibiting increased infarct volume after permanent proximal MCAO [41]. In “two kidneys, two clips” [40, 41] and “two kidneys, one clip” [41] rats, spontaneous cortical and subcortical ischemic infarcts, petechial brain hemorrhages of variable size, and dilated brain ventricles detected after 5-12 weeks. Spontaneous stroke not associated with overt neurological deficits |
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