Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice

Yoshizaki, Kaichi; Adachi, Kayo; Kataoka, Seiko; Watanabe, Atsushi; Tabira, Takeshi; Takahashi, K.; Wakita, Hideaki

doi:10.1016/j.expneurol.2007.12.005

Cited by 165 publications

(172 citation statements)

References 33 publications

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“…22 Moreover, periventricular white matter lesions are associated with reduced memory speed and performance, and the severity of the lesion can predict the evolution of cognitive decline. 23 In rats, recognition memory is compromised after lesion of the corpus callosum, 24 whereas recognition 25 and spatial memory 26 are impaired after chronic hypoperfusion in mice, along with decreased callosal fiber density. When challenged with chronic hypoperfusion, stroke-prone spontaneously hypertensive rats show diffuse tissue damage (white and grey matter, cortex, and hippocampus) and severe deficit in Morris water maze.…”

Section: Discussionmentioning

confidence: 99%

Recognition Memory Impairments After Subcortical White Matter Stroke in Mice

Blasi

Ying

Balkaya

et al. 2014

Stroke

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T he vast majority of experimental stroke research has focused on animal models of large territorial infarction involving both cortical and subcortical grey and white matter. 1 However, 20% to 25% of strokes in humans are small, lacunarlike, involve subcortical white matter tracts, 2 are often recurrent, and may lead to cognitive decline, subcortical dementia, and major disability. 3 Moreover, white matter ischemic lesions are a main pathological manifestation of small vessel diseases, a subset of cerebrovascular alterations leading to stroke and cognitive decline. 4 Only a few experimental models investigating small white matter strokes have been reported. 5 Recently, Carmichael and collaborators 6 developed a model of selective white matter stroke by injecting the potent vasoconstrictor endothelin-1 into corpus callosum to create a small area of myelin and axonal degeneration. Although reproducibility has been a problem with this model, it generates a lesion confined to white matter and therefore offer advantages to other white matter injury models that in addition cause diffuse brain injury after global cerebral hypoperfusion.7 After adapting, improving, and extending this new experimental approach, we tested whether subcortical white matter ischemic injury is associated with cognitive impairment in wildtype (WT) mice. Furthermore, we tested whether a NOTCH3 gene deletion negatively affects tissue and functional outcome after selective white matter injury. NOTCH3 mutations are the most common cause of inherited strokes and vascular dementia in young and middle-aged adults. 8 We previously showed that NOTCH3 knockout mice seem especially vulnerable to ischemic injury after middle cerebral artery occlusion, probably because of vascular dysfunction and reduced collateral blood flow. 9 Here, we extended these findings to white matter susceptibility and provided a novel experimental approach to further dissect the relationship between genotype and ischemic phenotype in NOTCH3 mutants. Materials and MethodsExperiments were conducted according to protocols approved by the Animal Research Committee of Massachusetts General Hospital and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (see online-only Data Supplement).Background and Purpose-Small subcortical white matter infarcts are a common stroke subtype often associated with cognitive deficits. The lack of relevant models confined to white matter has limited the investigation of its pathophysiology. Here, we examine tissue and functional outcome after an ischemic lesion within corpus callosum in wild-type (WT) mice and in mice null for a gene, NOTCH3, linked to white matter ischemic injury in patients. Methods-WT and NOTCH3 knockout mice were subjected to stereotactic microinjections of the potent vasoconstrictor endothelin-1 at the level of periventricular white matter to induce a focal ischemic lesion. Infarct location was confirmed by MRI, and brains were examined for lesion size and histology; behavioral deficits were a...

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Section: Discussionmentioning

confidence: 99%

Recognition Memory Impairments After Subcortical White Matter Stroke in Mice

Blasi

Ying

Balkaya

et al. 2014

Stroke

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“…Mice subjected to unilateral carotid artery occlusion had development of impaired object recognition and significant white matter damage in the corpus callosum and frontal-subcortical circuits; however, they maintained normal spontaneous activity. 6 Once their cerebral ischemia reached a severe degree (Ͻ10% supply), it caused a rapid loss of spine and dendrite microstructure within 10 minutes, which could be partially reversible only when reperfusion occurred within 20 to 60 minutes. 7 In the clinical scenario of carotid revascularization, a few studies showed that patients with severe asymptomatic ICA stenosis had cognitive improvements 3 months after carotid artery stenting (CAS), particularly in psychomotor processing speed; 8 -11 however, this conclusion is being debated because of lack of controls.…”

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confidence: 99%

“…[2][3][4] Moreover, severe ICA stenosis (Ն50%) has been associated with a higher prevalence of silent cerebral infarcts and white matter hyperintensities, 3 indicating that "asymptomatic" carotid stenosis may not be truly asymptomatic. To understand the pathological changes after chronic cerebral hypoperfusion, experimental models of vascular cognitive impairment have been induced by bilateral 5 or unilateral 6 common carotid artery occlusion. Mice subjected to unilateral carotid artery occlusion had development of impaired object recognition and significant white matter damage in the corpus callosum and frontal-subcortical circuits; however, they maintained normal spontaneous activity.…”

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confidence: 99%

Impairments in Cognitive Function and Brain Connectivity in Severe Asymptomatic Carotid Stenosis

Cheng

Lin

Soong

et al. 2012

Stroke

108

118

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Background and Purpose-Severe asymptomatic carotid stenosis has been associated with cognitive impairment, but it is unknown whether this association is attributable to effects on brain connectivity. We present cognitive network abnormalities in a group of patients at a presymptomatic stage. Methods-Seventeen patients with Ն70% asymptomatic stenosis of unilateral internal carotid artery were compared with 26 healthy controls utilizing a comprehensive neuropsychological battery, the dizziness handicap inventory, and multimodality neuroimaging including diffusion tensor imaging and resting-state functional connectivity magnetic resonance imaging. Longitudinally, assessments were completed in a subgroup of 10 patients at 3 months after carotid artery stenting. Results-Compared with the healthy controls, the patients had worse dizziness scores, poorer memory, complex visuo-spatial performances, and lower whole-brain mean fractional anisotropy. The Scheltens scores of leukoaraiosis/ infarction were not different between groups. Their seed-based functional connectivity magnetic resonance imaging showed marked decrements of interhemispheric and intrahemispheric, ipsilaterally to carotid stenosis, functional connectivity in the frontoparietal network. In the default mode network, the intrahemispheric functional connectivity was bilaterally impaired. Importantly, the disrupted mean fractional anisotropy in the patients significantly correlated with the attention and verbal memory functions. After successful carotid artery stenting, small but measurable increments of the mean fractional anisotropy and little functional connectivity in the default mode network ipsilateral-to-carotid artery stenting were noted. Conclusions-We identified for the first time distinct patterns of network disruption that correlate with cognitive fragility in patients with asymptomatic carotid stenosis. Brain connectivity may provide early and useful biomarkers for brain ischemia and reperfusion. (Stroke. 2012;43:2567-2573.)Key Words: asymptomatic carotid stenosis Ⅲ cognitive impairment Ⅲ diffusion tensor imaging Ⅲ endovascular treatment Ⅲ functional connectivity magnetic resonance imaging Ⅲ resting state Ⅲ stent A symptomatic stenosis of the internal carotid artery (ICA) is described as significant atherosclerosis without stroke or transient ischemic attack in the brain or eyes. 1 Retrospective studies comparing asymptomatic subjects with and without ultrasound-assessed carotid stenosis have shown that subjects with carotid stenosis had significantly poorer performance in tests of attention, psychomotor speed, and memory. [2][3][4] Moreover, severe ICA stenosis (Ն50%) has been associated with a higher prevalence of silent cerebral infarcts and white matter hyperintensities, 3 indicating that "asymptomatic" carotid stenosis may not be truly asymptomatic. To understand the pathological changes after chronic cerebral hypoperfusion, experimental models of vascular cognitive impairment have been induced by bilateral 5 or unilateral 6 common carotid a...

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“…Also, there is a 30% to 50% mortality rate in this model (9). Therefore, a new model of chronic cerebral hypoperfusion induced by unilateral common carotid artery occlusion (one-vessel occlusion, 1-VO) was introduced to simulate the chronic cerebral hypoperfusion in which animals developed cognitive decline (10). The chronic cerebral hypoperfusion induced by permanent right common carotid artery occlusion (RCCAO) was applied to both mice and rats which showed chronic mild reduction of cerebral blood flow with significant behavioral deficits.…”

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confidence: 99%

“…The chronic cerebral hypoperfusion induced by permanent right common carotid artery occlusion (RCCAO) was applied to both mice and rats which showed chronic mild reduction of cerebral blood flow with significant behavioral deficits. In addition, this cognitive impairment produced by RCCAO parallels with the patho-histological cerebral damage (10,11). However, the reproducibility of the 1-VO model presentation has not been examined by various laboratories.…”

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confidence: 99%

A Mouse Model for Chronic Cerebral Hypoperfusion-induced Cognitive Dysfunction

Li¹,

Zuo²

2017

J Anesth Perioper Med

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Background: Chronic cerebral hypoperfusion potentially contributes to the initiation and progression of vascular dementia (VD). Bilateral common carotid artery occlusion (two-vessel occlusion) is the most commonly used animal model to replicate this pathological condition but with high mortality and severe histological cerebral damage. Unilateral common carotid artery occlusion (one-vessel occlusion) was introduced to simulate clinical conditions. Our study was designed to further characterize this model. Methods: In this study, eight-week old CD -1 mice were subjected to left common carotid artery occlusion (LCCAO). Two weeks after the occlusion, their learning and memory were assessed by Barnes maze and fear conditioning. Histo-morphological changes were evaluated by Hematoxylin-Eosin staining. Neuronal and axonal degenerative changes were examined by amino-cupric sliver staining. Results: LCCAO increased the time to find the target box in the Barnes maze test during the 4-day training sessions and one day after the training sessions compared with sham group mice. There was no difference in context-related or tone-related freezing behavior between these two groups. No significant histological neuronal cell damage or degeneration was observed in brain sections of hippocampus and corpus callosum in these two groups. Conclusions: Our results suggest that LCCAO can be used to mimic the vascular dementia.

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Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice

Cited by 165 publications

References 33 publications

Recognition Memory Impairments After Subcortical White Matter Stroke in Mice

Recognition Memory Impairments After Subcortical White Matter Stroke in Mice

Impairments in Cognitive Function and Brain Connectivity in Severe Asymptomatic Carotid Stenosis

A Mouse Model for Chronic Cerebral Hypoperfusion-induced Cognitive Dysfunction

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