Related Experiment Video
Updated: Jan 18, 2026
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
Mouse models of vascular cognitive impairment and dementia induced by carotid artery manipulations: current status
Juyeon Mun1, Yorito Hattori2,3, Masafumi Ihara1,2
1Department of CADASIL Research and Development.
Insights
Three mouse models for vascular cognitive impairment and dementia (VCID) effectively mimic chronic cerebral hypoperfusion, aiding research into white matter lesions and executive dysfunction. These models advance understanding and therapeutic development for VCID.
Area of Science:
- Neuroscience
- Vascular Biology
- Animal Models
Background:
- Vascular cognitive impairment and dementia (VCID) is a significant health concern.
- Chronic cerebral hypoperfusion is a key pathological mechanism in VCID.
- Robust animal models are crucial for studying VCID mechanisms and testing therapeutics.
Purpose of the Study:
- To review three promising mouse models of VCID that replicate chronic cerebral hypoperfusion.
- To discuss therapeutic candidates evaluated in these models.
Main Methods:
- Focus on three mouse models: bilateral common carotid artery stenosis (BCAS), asymmetric common carotid artery surgery (ACAS), and gradual common carotid artery stenosis (GCAS).
- These models involve carotid artery manipulations to induce chronic cerebral hypoperfusion.
- Evaluation of model fidelity in recapitulating VCID hallmarks like white matter lesions and cognitive deficits.
Main Results:
- BCAS, ACAS, and GCAS models reproduce white matter lesions and executive dysfunction.
- ACAS and GCAS models better reflect gradual cerebral blood flow reduction and motor impairments compared to BCAS.
- ACAS uniquely shows subcortical small infarcts, a key feature of clinical VCID.
- These models elucidate VCID pathophysiology, including oligodendrocyte dysfunction, astrocytic dysfunction, and neuroinflammation.
- Therapeutic candidates like adrenomedullin and SIRT1 activators are under clinical investigation.
Conclusions:
- The three reviewed mouse models are valuable and complementary tools for studying VCID.
- These models have significantly advanced the understanding of VCID pathogenesis.
- They have facilitated the development of novel therapeutic strategies for VCID.
Purpose Of Review:
This review highlights three of the most promising mouse models of vascular cognitive impairment and dementia (VCID) that recapitulate chronic cerebral hypoperfusion. It also discusses therapeutic candidates evaluated using these models.
Recent Findings:
The three mouse models of chronic cerebral hypoperfusion induced by carotid artery manipulations are bilateral common carotid artery stenosis (BCAS), asymmetric common carotid artery surgery (ACAS), and gradual common carotid artery stenosis (GCAS). Altogether, these models reproduce white matter lesions and executive dysfunction. Notably, ACAS and GCAS exhibit gradual cerebral blood flow (CBF) reduction and motor impairments, addressing key limitations of BCAS, which induces abrupt CBF decrease and no motor deficits. Furthermore, ACAS uniquely demonstrates subcortical small infarcts, a hallmark feature of clinical VCID. These models have greatly contributed to elucidating VCID pathophysiology, including abnormal oligodendrocyte maturation, astrocytic dysfunction, and neuroinflammation. Several therapeutic strategies developed using these models - such as adrenomedullin and SIRT1 activator - are currently under investigation in clinical trials.
Summary:
The three models are robust and complementary tools for exploring the VCID mechanisms. They have been instrumental in advancing our understanding of VCID pathogenesis and in facilitating the development of novel therapeutic approaches.
