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| Animal model | Blood cholesterol concentrations | Systemic vascular pathology | Cerebrovascular features |
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| ApoE-/- mouse | Increased 4.3-8 times on regular diet, elevated additional 1.4-2.7 times on high-cholesterol diet [7, 8] | Fatty streaks in aortic wall and extracranial carotid arteries after 6 weeks that are exacerbated by high-cholesterol diet and then associated with lipid deposition in brain arterioles [7, 9]. Upon high-cholesterol diet atherosclerotic plaque formation within 6 months [9] | Infarct volume, blood-brain barrier permeability, and neurological deficits after transient proximal MCAO or transient distal MCAO increased in ApoE-/- mice on high-cholesterol diet [7–10]. Vasorelaxation and VEGF-induced angiogenesis were compromised, resulting in reduced cerebral blood flow [7–11]. Increase of infarct volume and blood-brain barrier permeability mediated by RhoA overactivation and brain neutrophil invasion [7, 8, 10] |
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| LDL receptor-/- mouse | Increased 1.9-2.4 times on regular diet, elevated additional 1.5 times on high-cholesterol diet [12] | Little vascular abnormalities under normal diet [12]. Upon high-cholesterol diet, atherosclerotic plaque formation in aortic wall and coronary arteries after 5-7 months [12] | Thrombotic occlusions of cerebral microvessels and occasional microhemorrhages in LDL receptor-/- mice on high-cholesterol diet at ~6 months [14]. Infarct volume after transient proximal MCAO unaffected by LDL receptor-/- [16]. Platelet deactivation by antiglycoprotein-Ib and antiglycoprotein-VI antibody reduced infarct volume and neurological deficits in 12-month-old LDL receptor-/- and wild-type mice without increasing hemorrhagic transformation [16]. Glycoprotein-IIb/IIIa inhibition had no effect [16] |
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| Human ApoB transgenic (hApoBTg) mouse | Increased 1.3-1.8 times on regular diet, elevated additional 2.2 times on high-cholesterol diet [13] | Little vascular abnormalities under normal diet [13]. Upon high-cholesterol diet, atherosclerotic plaque formation in aortic wall that is more severe in female than male mice after 4 months [13] | Brain capillary density reduced in hApoBTg mice upon high-cholesterol diet after ~6 months, suggestive of spontaneous microvascular occlusions [15]. Microvascular injury after unilateral common carotid artery occlusion not influenced by transgenic ApoB in mice exposed to high-cholesterol diet [15] |
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| High-cholesterol diet in wild-type mouse | Increased 2.2-3.9 times in C57BL6 mouse [11, 13] | Modest fatty streaks in the aorta even after several months of high-cholesterol diet [13]. Metabolic syndrome characterized by obesity, type-2 diabetes, and hypercholesterolemia [23] with lipid deposition in cerebral arterioles [7] | Blood-brain barrier permeability, calpain-1/2 activity, matrix metalloproteinase-2/9 activity, and brain edema after transient proximal MCAO increased in C57BL6 mice on high-cholesterol diet presumably due to RhoA overactivation [7]. Infarct volume and neuronal injury unchanged [7, 11] |
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| High-cholesterol diet in rat | Increased 2.1-4.2 times in Sprague-Dawley rat [26, 27] | Modest fatty streaks in the aorta even after several months of high-cholesterol diet [26, 27] | Infarct volume, blood-brain barrier permeability, brain edema, brain lipid peroxidation, and brain leukocyte infiltration after transient proximal MCAO increased in Sprague-Dawley rats on high-cholesterol diet [26, 27]. Changes prevented by simvastatin and ginkgolide-B [26] |
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| High-cholesterol diet in rabbit | LDL increased 34.7 times [28] | Atheromas of internal carotid and basilar arteries after 5 weeks of high-cholesterol diet [28] | Number of hemorrhagic infarcts reduced, but infarct size increased in rabbits on high-cholesterol diet exposed to focal cerebral ischemia induced by sephadex-G75 polymer [28]. Increased infarct size associated with accumulation of platelet-rich thrombi in infarct foci [28] |
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