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Updated: Apr 16, 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
A novel mouse model of subcortical infarcts with dementia
Yorito Hattori1, Jun-ichiro Enmi2, Akihiro Kitamura3
1Departments of Regenerative Medicine and.
Abstract:
Subcortical white matter (WM) is a frequent target of ischemic injury and extensive WM lesions are important substrates of vascular cognitive impairment (VCI) in humans. However, ischemic stroke rodent models have been shown to mainly induce cerebral infarcts in the gray matter, while cerebral hypoperfusion models show only WM rarefaction without infarcts. The lack of animal models consistently replicating WM infarct damage may partially explain why many neuroprotective drugs for ischemic stroke or VCI have failed clinically, despite earlier success in preclinical experiments. Here, we report a novel animal model of WM infarct damage with cognitive impairment can be generated by surgical implantation of different devices to the right and left common carotid artery (CCA) in C57BL/6J mice. Implantation of an ameroid constrictor to the right CCA resulted in gradual occlusion of the vessel over 28 d, whereas placement of a microcoil to the left CCA induced ∼50% arterial stenosis. Arterial spin labeling showed a gradual reduction of cerebral blood flow over 28 d post operation. Such reductions were more marked in the right, compared with the left, hemisphere and in subcortical, rather than the cortical, areas. Histopathological analysis showed multiple infarct damage in right subcortical regions, including the corpus callosum, internal capsule, hippocampal fimbria, and caudoputamen, in 81% of mice. Mice displaying such damage performed significantly poorer in locomotor and cognitive tests. The current mouse model replicates the phenotypes of human subcortical VCI, including multiple WM infarcts with motor and cognitive impairment.
Insights
Researchers developed a new mouse model for subcortical white matter (WM) damage, mimicking vascular cognitive impairment (VCI). This model shows WM infarcts and cognitive deficits, crucial for studying VCI treatments.
Area of Science:
- Neuroscience
- Vascular Biology
- Animal Models
Background:
- Subcortical white matter (WM) lesions are key in vascular cognitive impairment (VCI).
- Existing rodent models fail to consistently replicate WM infarcts, hindering VCI drug development.
- Current models primarily show gray matter damage or WM rarefaction without infarcts.
Purpose of the Study:
- To establish a novel rodent model that accurately replicates subcortical WM infarct damage and associated cognitive impairment.
- To provide a preclinical tool for evaluating neuroprotective strategies against VCI.
- To investigate the effects of induced hypoperfusion on specific brain regions.
Main Methods:
- Surgical implantation of an ameroid constrictor and a microcoil into the common carotid arteries (CCAs) of C57BL/6J mice.
- Utilized arterial spin labeling to monitor cerebral blood flow changes over 28 days.
- Conducted histopathological analysis and locomotor/cognitive behavioral tests.
Main Results:
- The surgical procedure induced gradual occlusion and stenosis in the CCAs, leading to reduced cerebral blood flow, particularly in subcortical areas.
- Histopathology revealed multiple WM infarcts in 81% of mice, affecting regions like the corpus callosum and internal capsule.
- Mice with WM infarcts exhibited significant deficits in motor function and cognitive performance.
Conclusions:
- The developed mouse model successfully replicates key features of human subcortical VCI, including WM infarcts and cognitive/motor impairments.
- This model offers a valuable platform for preclinical research into VCI pathogenesis and therapeutic interventions.
- The findings highlight the importance of subcortical WM integrity in maintaining cognitive function.
