A novel mouse model of ischemic carotid artery disease

PLoS One. 2014 Jun 18;9(6):e100257. doi: 10.1371/journal.pone.0100257. eCollection 2014.

Abstract

Background: Carotid artery occlusive disease gradually develops over time, eventually leading to cerebral infarction and high mortality rate. Animal models replicating cerebral infarction resulting from carotid artery occlusive disease have thus been developed to test potential novel treatments, which could be subsequently administered clinically.

Methods: Adult C57BL/6J male mice were subjected to ameroid constrictor (AC) placement to gradually narrow the bilateral common carotid arteries. Cerebral blood flow (CBF) was measured at several time points. At 7 and 28 days post-operation, post-mortem brain samples were analyzed for ischemic changes.

Results: The mortality rate was 58.8% at 28 days post-operation. Surviving mice with AC showed continuous reduction of CBF by up to 70% of the baseline level at 28 days. Most of the mice (75%) showed multiple cerebral infarctions in the gray and white matter. Non-surviving mice showed critical CBF reduction below 20-30% of the baseline level before death.

Conclusion: The application of the AC on the bilateral common carotid arteries in mice could offer a reliable model of severe cerebrovascular insufficiency due to carotid artery occlusive disease and may thus be useful in exploring pharmacological intervention in stroke through monitoring survival rate, infarct formation, and CBF profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity
  • Brain / blood supply
  • Brain / pathology
  • Brain / physiopathology
  • Carotid Artery, Common / pathology*
  • Carotid Artery, Common / physiopathology
  • Carotid Artery, Common / surgery
  • Carotid Stenosis / complications
  • Carotid Stenosis / mortality
  • Carotid Stenosis / pathology*
  • Carotid Stenosis / physiopathology
  • Cerebral Infarction / etiology
  • Cerebral Infarction / mortality
  • Cerebral Infarction / pathology*
  • Cerebral Infarction / physiopathology
  • Cerebrovascular Circulation
  • Disease Models, Animal*
  • Humans
  • Ischemia / complications
  • Ischemia / mortality
  • Ischemia / pathology*
  • Ischemia / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Regional Blood Flow
  • Survival Analysis

Grants and funding

The authors have grant support from the Ministry of Health, Labor and Welfare (M.I., No. 0605-1) and the Takeda Science Foundation (M.I.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.