Related Experiment Video
Updated: Oct 31, 2025
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
Cardiac Dysfunction in a Mouse Vascular Dementia Model of Bilateral Common Carotid Artery Stenosis
Lulu An1, Michael Chopp1,2, Alex Zacharek1
1Department of Neurology, Henry Ford Hospital, Detroit, MI, United States.
Insights
Bilateral common carotid artery stenosis (BCAS) in mice induces cognitive deficits and cardiac dysfunction. This vascular dementia model causes heart hypertrophy, fibrosis, inflammation, and oxidative stress, linking brain and heart health.
Area of Science:
- Cardiovascular Science
- Neuroscience
- Pathology
Background:
- Cardiac function is intrinsically linked to cognitive function.
- Previous research demonstrated that stroke and traumatic brain injury precipitate cardiac dysfunction in mice.
- This study investigates if bilateral common carotid artery stenosis (BCAS), a model for vascular dementia (VaD), also induces cardiac dysfunction.
Purpose of the Study:
- To determine if BCAS, a model of vascular dementia, induces cardiac dysfunction in mice.
- To explore the relationship between cognitive deficits and cardiac dysfunction in the BCAS model.
- To investigate the underlying mechanisms of BCAS-induced cardiac dysfunction, including inflammation and oxidative stress.
Main Methods:
- Adult C57BL/6J mice underwent sham surgery or BCAS using microcoils.
- Cerebral blood flow and cognitive function were assessed post-BCAS.
- Echocardiography, cardiac tissue analysis (histochemistry, gene expression), and biochemical assays were performed.
Main Results:
- BCAS induced significant cerebral hypoperfusion and cognitive dysfunction.
- BCAS led to cardiac hypertrophy, left ventricular enlargement, and impaired cardiac function (reduced LVEF, LVFS).
- Increased cardiac fibrosis, oxidative stress (4-HNE, NOX2), inflammation (leukocyte/macrophage infiltration, IL-6), and thrombin expression were observed.
Conclusions:
- BCAS in mice, without pre-existing cardiac disease, provokes cardiac dysfunction.
- The cardiac dysfunction observed in the BCAS model is partly mediated by increased inflammation and oxidative stress.
- This study highlights a connection between vascular dementia induction and subsequent cardiac pathology.
Abstract:
Background: Cardiac function is associated with cognitive function. Previously, we found that stroke and traumatic brain injury evoke cardiac dysfunction in mice. In this study, we investigate whether bilateral common carotid artery stenosis (BCAS), a model that induces vascular dementia (VaD) in mice, induces cardiac dysfunction. Methods: Late-adult (6-8 months) C57BL/6J mice were subjected to sham surgery (n = 6) or BCAS (n = 8). BCAS was performed by applying microcoils (0.16 mm internal diameter) around both common carotid arteries. Cerebral blood flow and cognitive function tests were performed 21-28 days post-BCAS. Echocardiography was conducted in conscious mice 29 days after BCAS. Mice were sacrificed 30 days after BCAS. Heart tissues were isolated for immunohistochemical evaluation and real-time PCR assay. Results: Compared to sham mice, BCAS in mice significantly induced cerebral hypoperfusion and cognitive dysfunction, increased cardiac hypertrophy, as indicated by the increased heart weight and the ratio of heart weight/body weight, and induced cardiac dysfunction and left ventricular (LV) enlargement, indicated by a decreased LV ejection fraction (LVEF) and LV fractional shortening (LVFS), increased LV dimension (LVD), and increased LV mass. Cognitive deficits significantly correlated with cardiac deficits. BCAS mice also exhibited significantly increased cardiac fibrosis, increased oxidative stress, as indicated by 4-hydroxynonenal and NADPH oxidase-2, increased leukocyte and macrophage infiltration into the heart, and increased cardiac interleukin-6 and thrombin gene expression. Conclusions: BCAS in mice without primary cardiac disease provokes cardiac dysfunction, which, in part, may be mediated by increased inflammation and oxidative stress.
