Dataset Information

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans.

ABSTRACT:

Background

Existing rodent models of vascular cognitive impairment (VCI) show abrupt changes in cerebral blood flow (CBF) and do not reliably replicate the clinical pathogenesis of VCI. We therefore aimed to develop a mouse model of VCI where CBF is gradually reduced, followed by subsequent progressive motor and cognitive impairment, after surgical intervention.

Methods and results

Adult C57BL/6J male mice were subjected to gradual common carotid artery stenosis (GCAS) surgery by using an ameroid constrictor vessel-constricting device with an inner diameter of 0.75 mm. The common carotid arteries narrowed gradually after gradual constriction of ameroid constrictors over 28 days after GCAS, with subsequent 79.3% area stenosis as a result of smooth muscle cell proliferation and macrophage infiltration in the tunica intima. The 28-day survival rate was 91%. Arterial spin labeling demonstrated gradual and continuous reduction of cortical and subcortical CBF (ratio to the preoperative value) to 54.6% and 51.5%, respectively, over 28 days. However, magnetic resonance angiography showed increment of collateral flow signals in the leptomeningeal artery. Rarefaction and proliferation of astrocytes and microglia, with loss of oligodendrocytes, were found in the white matter at 32 days. Hippocampal neuronal loss was observed in only 25% of GCAS mice, consistent with lack of abnormalities in the Morris water maze test. The rotarod test showed motor impairment, and the Y-maze test showed working memory deficits.

Conclusions

The GCAS model successfully generated gradual and continuous CBF reduction over 28 days, with replication of key histological, radiological, and behavioral features associated with cerebral hypoperfusion leading to VCI.

SUBMITTER: Hattori Y

PROVIDER: S-EPMC4802480 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans.

Hattori Yorito Y Enmi Jun-Ichiro J Iguchi Satoshi S Saito Satoshi S Yamamoto Yumi Y Tsuji Masahiro M Nagatsuka Kazuyuki K Kalaria Rajesh N RN Iida Hidehiro H Ihara Masafumi M

Journal of the American Heart Association 20160222 2

<h4>Background</h4>Existing rodent models of vascular cognitive impairment (VCI) show abrupt changes in cerebral blood flow (CBF) and do not reliably replicate the clinical pathogenesis of VCI. We therefore aimed to develop a mouse model of VCI where CBF is gradually reduced, followed by subsequent progressive motor and cognitive impairment, after surgical intervention.<h4>Methods and results</h4>Adult C57BL/6J male mice were subjected to gradual common carotid artery stenosis (GCAS) surgery by ...[more]

PMID: 26903005

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Project description:Background: Risk stratification of asymptomatic carotid artery stenosis (ACAS) is still an issue for carotid revascularization. We sought to identify factors associated with symptomatic carotid artery stenosis (SCAS) using multimodal imaging techniques. Methods: We retrospectively collected data on patients who underwent carotid artery revascularization. Results from duplex sonography, computerized tomography angiography, brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), perfusion-weighted imaging, and demographic profiles were compared between ACAS and SCAS patients. Differences in baseline characteristics between the two groups were balanced by the propensity matching score method. Multivariable regression analysis was performed to identify factors associated with symptomaticity of carotid artery stenosis. We compared the strength of associations between significant imaging factors and symptomatic carotid stenosis using C statistics. Results: A total of 259 patients (asymptomatic 57.1%, symptomatic 42.9%) with carotid stenosis were included. After 1:1 propensity score matching, the multivariable regression analysis revealed that the absence of plaque calcification [Odds ratio 0.41, 95% confidence interval (CI) 0.182-0.870, p = 0.023], deep white matter hyperintensity (DWMH; Odds ratio 3.46, 95% CI 1.842-6.682, p < 0.001), susceptibility vessel sign seen on gradient-echo MRI (Odds ratio 2.35, 95% CI 1.113-5.107, p = 0.027), and increased cerebral blood volume (CBV) seen on perfusion-weighted MRI (CBV; Odds ratio 2.17, 95% CI 1.075-4.454, p = 0.032) were associated with SCAS. The combination of these variables had a fair accuracy to classify SCAS (Area under the curve 0.733, 95% CI 0.662-0.803). Conclusions: We identified several multimodal imaging markers independently associated with SCAS. These markers may provide information to identify ACAS patients with high risk of ischemic stroke. Future studies are needed to predict SCAS using our findings in other independent cohorts.

Project description:Patients with contralateral carotid occlusion (CCO) have been excluded from randomized clinical trials because of a deemed high risk for adverse neurologic outcomes with carotid endarterectomy (CEA). Evidence for this rationale is limited and conflicting. Therefore, we aimed to compare outcomes after CEA between patients with and without CCO and varying degrees of contralateral carotid stenosis (CCS).We identified patients undergoing CEA from 2003 to 2015 in the Vascular Study Group of New England (VSGNE) registry. Patients were stratified by preoperative symptom status and presence of CCO. Multivariable analysis was used to account for differences in demographics and comorbidities. Our primary outcome was 30-day stroke/death risk.Of 15,487 patients we identified who underwent CEA, 10,377 (67%) were asymptomatic. CCO was present in 914 patients, of whom 681 (75%) were asymptomatic. Overall, the 30-day stroke/death was 2.0% for symptomatic patients (CCO: 2.6%) and 1.1% for asymptomatic patients (CCO: 2.3%). After adjustment, including symptom status, CCO was associated with higher 30-day stroke/death (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.4-3.3; P = .001), any in-hospital stroke (OR, 2.8; 95% CI, 1.7-4.6; P < .001), in-hospital ipsilateral stroke (OR, 2.2; 95% CI, 1.2-4.0; P = .02), in-hospital contralateral stroke (OR, 5.1; 95% CI, 2.2-11.4; P < .001), and prolonged length of stay (OR, 1.6; 95% CI, 1.3-1.9; P < .001). CCS of 80% to 99% was only associated with a prolonged length of stay (OR, 1.3; 95% CI, 1.1-1.6; P = .01), not with in-hospital stroke. Neither CCO nor CCS was associated with 30-day mortality.Although CCO increases the risk of 30-day stroke/death, in-hospital strokes, and prolonged length of stay after CEA, the 30-day stroke/death rates in symptomatic and asymptomatic patients with CCO remain within the recommended thresholds set by the 14 societies' guideline document. Thus, CCO should not qualify as a high-risk criterion for CEA. Moreover, there is no evidence that patients with CCO have lower stroke/death rates after carotid artery stenting than after CEA. We believe that CEA remains a valid and safe option for patients with CCO and that CCO should not be applied as a criterion to promote carotid artery stenting per se.

Dataset Information

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans.

Background

Methods and results

Conclusions

Publications

Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans.

Similar Datasets

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