A mouse model characterizing features of vascular dementia with hippocampal atrophy

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

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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 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, 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.

Original languageEnglish
Pages (from-to)1278-1284
Number of pages7
JournalStroke
Volume41
Issue number6
DOIs
Publication statusPublished - 01-06-2010

Fingerprint

Vascular Dementia
Carotid Stenosis
Atrophy
Cerebrovascular Circulation
Short-Term Memory
Positron-Emission Tomography
Rheology
Memory Disorders
Cerebral Cortex
Lasers
Glucose

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Nishio, K., Ihara, M., Yamasaki, N., Kalaria, R. N., Maki, T., Fujita, Y., ... Tomimoto, H. (2010). A mouse model characterizing features of vascular dementia with hippocampal atrophy. Stroke, 41(6), 1278-1284. https://doi.org/10.1161/STROKEAHA.110.581686
Nishio, Keiko ; Ihara, Masafumi ; Yamasaki, Nobuyuki ; Kalaria, Raj N. ; Maki, Takakuni ; Fujita, Youshi ; Ito, Hidefumi ; Oishi, Naoya ; Fukuyama, Hidenao ; Miyakawa, Tsuyoshi ; Takahashi, Ryosuke ; Tomimoto, Hidekazu. / A mouse model characterizing features of vascular dementia with hippocampal atrophy. In: Stroke. 2010 ; Vol. 41, No. 6. pp. 1278-1284.
@article{19834c17e7ea4159924082c0b00ab16c,
title = "A mouse model characterizing features of vascular dementia with hippocampal atrophy",
abstract = "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 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, 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.",
author = "Keiko Nishio and Masafumi Ihara and Nobuyuki Yamasaki and Kalaria, {Raj N.} and Takakuni Maki and Youshi Fujita and Hidefumi Ito and Naoya Oishi and Hidenao Fukuyama and Tsuyoshi Miyakawa and Ryosuke Takahashi and Hidekazu Tomimoto",
year = "2010",
month = "6",
day = "1",
doi = "10.1161/STROKEAHA.110.581686",
language = "English",
volume = "41",
pages = "1278--1284",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

Nishio, K, Ihara, M, Yamasaki, N, Kalaria, RN, Maki, T, Fujita, Y, Ito, H, Oishi, N, Fukuyama, H, Miyakawa, T, Takahashi, R & Tomimoto, H 2010, 'A mouse model characterizing features of vascular dementia with hippocampal atrophy', Stroke, vol. 41, no. 6, pp. 1278-1284. https://doi.org/10.1161/STROKEAHA.110.581686

A mouse model characterizing features of vascular dementia with hippocampal atrophy. / Nishio, Keiko; Ihara, Masafumi; Yamasaki, Nobuyuki; Kalaria, Raj N.; Maki, Takakuni; Fujita, Youshi; Ito, Hidefumi; Oishi, Naoya; Fukuyama, Hidenao; Miyakawa, Tsuyoshi; Takahashi, Ryosuke; Tomimoto, Hidekazu.

In: Stroke, Vol. 41, No. 6, 01.06.2010, p. 1278-1284.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A mouse model characterizing features of vascular dementia with hippocampal atrophy

AU - Nishio, Keiko

AU - Ihara, Masafumi

AU - Yamasaki, Nobuyuki

AU - Kalaria, Raj N.

AU - Maki, Takakuni

AU - Fujita, Youshi

AU - Ito, Hidefumi

AU - Oishi, Naoya

AU - Fukuyama, Hidenao

AU - Miyakawa, Tsuyoshi

AU - Takahashi, Ryosuke

AU - Tomimoto, Hidekazu

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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 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, 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.

AB - 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 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, 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.

UR - http://www.scopus.com/inward/record.url?scp=77953138856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953138856&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.110.581686

DO - 10.1161/STROKEAHA.110.581686

M3 - Article

C2 - 20448204

AN - SCOPUS:77953138856

VL - 41

SP - 1278

EP - 1284

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 6

ER -

Nishio K, Ihara M, Yamasaki N, Kalaria RN, Maki T, Fujita Y et al. A mouse model characterizing features of vascular dementia with hippocampal atrophy. Stroke. 2010 Jun 1;41(6):1278-1284. https://doi.org/10.1161/STROKEAHA.110.581686