Pre-clinical models of human cerebral small vessel disease: Utility for clinical application

Hainsworth, Atticus H.; Brittain, John F.; Khatun, Halima

doi:10.1016/j.jns.2012.05.046

Cited by 30 publications

(25 citation statements)

References 69 publications

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“…Blood-borne CD45-positive leukocytes were found distributed in the brain of SHR compared to controls indicating neuroinflammatory contributions to the development of cSVD (Kaiser et al 2014). BBB breakdown, evident by the leakage of immunoglobulin G (IgG) and dextran, as well as platelet aggregation in the vicinity of vascular stasis has been observed (Hainsworth et al 2012;Holland et al 2015). Furthermore, ultrastructural changes to astrocyte endfeet in the SHR model were indicative of gliovascular changes.…”

Section: Cerebral Small Vessel Disease Modelmentioning

confidence: 98%

Animal Models of Vascular Cognitive Impairment and Dementia (VCID)

Gooch

Wilcock

2016

Cell Mol Neurobiol

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Although SHRSP develop severe hypertension, milder chronic hypertension is induced by supplementing drinking water with the NOS-inhibitor L-N-Nitroarginine methyl ester, 39 or chronic infusion of angiotensin II by minipump. 40 Mice receiving a subpressor infusion of angiotensin II develop mild hypertension (mean arterial blood pressure 90 mm Hg, relative to 70 mm Hg in saline-infused controls). 40 In addition to vascular actions, subpressor concentrations of the hyper-tensive agent may have direct effects on neural organization and metabolism. Hyperhomocysteinemia in Mice and Rats Elevated plasma concentration of the nonessential amino acid homocysteine, termed hyperhomocysteinemia, is a risk factor for VCID. 41 In wild-type mice, a diet deficient in 3 B vitamins (B6, B9-folate, and B12) resulted in hyperhomocysteinemia within 10 weeks, accompanied by reduced capillary density in brain tissue and impaired performance in Morris water maze.

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Section: Cerebral Small Vessel Disease Modelmentioning

confidence: 98%

Animal Models of Vascular Cognitive Impairment and Dementia (VCID)

Gooch

Wilcock

2016

Cell Mol Neurobiol

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“…Surgical animal models, such as the bilateral common carotid artery stenosis hypoperfusion mouse model, the transverse aortic constriction model, and myocardial infarction models, display the key features of vascular cognitive impairment. 105,106 Observations from epidemiological and pathological studies challenge the conventional distinction between AD and VaD, as defined by diagnostic criteria. In a community-based neuropathological study, AD-type and vascular pathology were the main pathological corre lates of dementia in elderly people, although most patients had mixed disease.…”

Section: Wmhs and The Development Of Dementiamentioning

confidence: 99%

White matter hyperintensities, cognitive impairment and dementia: an update

2015

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White matter hyperintensities (WMHs) in the brain are the consequence of cerebral small vessel disease, and can easily be detected on MRI. Over the past three decades, research has shown that the presence and extent of white matter hyperintense signals on MRI are important for clinical outcome, in terms of cognitive and functional impairment. Large, longitudinal population-based and hospital-based studies have confirmed a dose-dependent relationship between WMHs and clinical outcome, and have demonstrated a causal link between large confluent WMHs and dementia and disability. Adequate differential diagnostic assessment and management is of the utmost importance in any patient, but most notably those with incipient cognitive impairment. Novel imaging techniques such as diffusion tensor imaging might reveal subtle damage before it is visible on standard MRI. Even in Alzheimer disease, which is thought to be primarily caused by amyloid, vascular pathology, such as small vessel disease, may be of greater importance than amyloid itself in terms of influencing the disease course, especially in older individuals. Modification of risk factors for small vessel disease could be an important therapeutic goal, although evidence for effective interventions is still lacking. Here, we provide a timely Review on WMHs, including their relationship with cognitive decline and dementia.

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“…From 7 days post-occlusion these animals developed progressive white matter pallor and vacuolation in the corpus callosum, deep subcortical and periventricular white matter areas, with some demyelination, up to sacrifice at 28 days 13 . While a primate surgical model poses substantial logistic challenges, data from a human-like experimental species with extensive white matter are uniquely valuable 7, 32, 33 . For VCID-relevant research, it is notable that ageing baboons exhibit both β-amyloid and tau neuropathology.…”

Section: Hypoperfusion: Baboonsmentioning

confidence: 99%

“…The limitations of animal models for VCID are well-known 1, 7, 8 . Experimental species differ from humans in terms of lifespan, relative white matter abundance, large artery dimensions (Figure 1) and in size and morphology of deep penetrating arteries (Figure 2).…”

Section: Introductionmentioning

confidence: 99%