title: Motor and cognitive impairment in a mouse model of ischemic carotid artery disease.
abstract: We have recently established a novel mouse model of bilateral common carotid artery gradual occlusion. This model serves as a mimic of severe carotid artery disease with multiple cerebral infarctions induced by cerebrovascular insufficiency. In this study, we examined whether locomotor and cognitive impairment was induced in these mice using a test battery for neurological and cognitive functions. Adult C57BL/6J male mice were subjected to either ameroid constrictor (AC) placement to gradually narrow the bilateral common carotid arteries or to sham surgery. At 28 days post-surgery, locomotor activity was assessed by rotarod and wire hang tests, and cognitive function was assessed using the Y-maze and Morris water maze tests. Rotarod and wire hang tests showed a significantly shorter latency to fall in mice subjected to the placement of ACs compared with sham surgery mice. AC-implanted mice showed significant impairments in working memory on the Y-maze test and in spatial learning and reference memory on the Morris water maze test. Therefore, the current mouse model with AC placement on the bilateral common carotid arteries showed locomotor disability, learning deficits, and memory impairment, which well-replicated the outcomes of patients with ischemic carotid artery disease. This model will be useful for investigating the mechanisms underlying the neurological and cognitive deficits following cerebrovascular insufficiency and for exploring pharmacological interventions for stroke patients with severe carotid artery disease.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Yorito
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kitamura
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagatsuka
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan; Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. Electronic address: ihara@ncvc.go.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D002340:Carotid Artery Diseases / Q000150:complications* / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D053208:Kaplan-Meier Estimate; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000209:etiology* / Q000503:physiopathology; D045442:Rotarod Performance Test
keywords: Carotid artery disease; Cerebral infarction; Cognitive impairment; Dementia; Motor incoordination; Muscle weakness