Document Detail


A mouse model characterizing features of vascular dementia with hippocampal atrophy.
MedLine Citation:
PMID:  20448204     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: We have previously described effects of chronic cerebral hypoperfusion in mice with bilateral common carotid artery stenosis (BCAS) using microcoils for 30 days. These mice specifically exhibit working memory deficits attributable to frontal-subcortical circuit damage without apparent gray matter changes, indicating similarities with subcortical ischemic vascular dementia. However, as subcortical ischemic vascular dementia progresses over time, the longer-term effects that characterize the mouse model are not known. METHODS: Comprehensive behavioral test batteries and histological examinations were performed in mice subjected to BCAS for up to 8 months. Laser speckle flowmetry and (18)F-fluorodeoxyglucose positron emission tomography were performed to assess cerebral blood flow and metabolism at several time points. RESULTS: At 2 hours after BCAS, cerebral blood flow in the cerebral cortex temporarily decreased to as much as 60% to 70% of the control value but gradually recovered to >80% at 1 to 3 months. At 5 to 6 months after BCAS, reference and working memory were impaired as demonstrated by the Barnes and radial arm maze tests, respectively. Furthermore, (18)F-fluorodeoxyglucose positron emission tomography demonstrated that hippocampal glucose utilization was impaired at 6 months after BCAS. Consistent with these behavioral and metabolic abnormalities, histological analyses demonstrated hippocampal atrophy with pyknotic and apoptotic cells at 8 months after BCAS. CONCLUSIONS: These results suggest that the longer-term BCAS model replicates advanced stages of subcortical ischemic vascular dementia when hippocampal neuronal loss becomes significant.
Authors:
Keiko Nishio; Masafumi Ihara; Nobuyuki Yamasaki; Raj N Kalaria; Takakuni Maki; Youshi Fujita; Hidefumi Ito; Naoya Oishi; Hidenao Fukuyama; Tsuyoshi Miyakawa; Ryosuke Takahashi; Hidekazu Tomimoto
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Publication Detail:
Type:  Journal Article     Date:  2010-05-06
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  41     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-06-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1278-84     Citation Subset:  IM    
Affiliation:
Department of Neurology, Faculty of Medicine, Kyoto University, Sakyo-Ku, Kyoto 606-8507 Japan. ihara@kuhp.kyoto-u.ac.jp.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Atrophy
Behavior, Animal*
Carotid Artery, Common / physiopathology,  radiography
Carotid Stenosis* / complications,  physiopathology,  radiography
Cerebrovascular Circulation
Dementia, Vascular* / etiology,  physiopathology,  radiography
Disease Models, Animal
Fluorodeoxyglucose F18 / pharmacology
Hippocampus* / physiopathology,  radiography
Male
Maze Learning*
Mice
Positron-Emission Tomography*
Radiopharmaceuticals / pharmacology
Chemical
Reg. No./Substance:
0/Radiopharmaceuticals; 63503-12-8/Fluorodeoxyglucose F18

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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