Related Experiment Video
Updated: Mar 6, 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
Protocol for mouse vascular dementia model and evaluation of progressive tissue damage in subcortical white matter
Min Tian1, Irene L Llorente2, S Thomas Carmichael3
1Bioscience and Biomedical Engineering Thrust, The Brain and Intelligence Research Institute, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511400, China.
Abstract:
Here, we present a protocol for generating a vascular dementia (VaD) mouse model through stereotaxic microinjection of a vasoconstrictor into the subcortical white matter (WM). We describe steps for preparing the N5-(1-iminoethyl)-L-ornithine (L-NIO) solution, surgical procedures, and immunohistochemistry. We then detail procedures for confocal imaging and image analysis using ImageJ and Imaris software to evaluate key pathological features of human VaD, including vessel dilation, demyelination, glial reactivity, neuronal damage, subcortical WM atrophy, and ventriculomegaly. For complete details on the use and execution of this protocol, please refer to Tian et al.1.
Insights
This study details a new protocol for creating a vascular dementia (VaD) mouse model. The method uses microinjection to replicate key VaD pathologies in the brain's white matter.
Area of Science:
- Neuroscience
- Pathology
- Animal Models
Background:
- Vascular dementia (VaD) is a significant cause of cognitive impairment.
- Existing models may not fully capture the complexity of human VaD pathology.
- A reliable animal model is crucial for understanding VaD pathogenesis and testing therapies.
Purpose of the Study:
- To present a detailed protocol for generating a mouse model of vascular dementia (VaD).
- To establish a reproducible method for inducing subcortical white matter (WM) damage relevant to VaD.
- To outline techniques for evaluating key pathological hallmarks of VaD in the generated model.
Main Methods:
- Stereotaxic microinjection of N5-(1-iminoethyl)-L-ornithine (L-NIO), a vasoconstrictor, into the subcortical white matter (WM) of mice.
- Detailed surgical procedures, including solution preparation and stereotaxic targeting.
- Immunohistochemistry, confocal imaging, and quantitative image analysis using ImageJ and Imaris software.
Main Results:
- Successful generation of a mouse model exhibiting key pathological features of human VaD.
- Demonstration of vessel dilation, demyelination, glial reactivity, neuronal damage, subcortical WM atrophy, and ventriculomegaly.
- Validation of the protocol's ability to induce and assess specific VaD-related neuropathologies.
Conclusions:
- The presented protocol provides a robust method for creating a VaD mouse model.
- This model facilitates the study of VaD pathophysiology and the evaluation of potential therapeutic interventions.
- The protocol enables comprehensive analysis of critical pathological markers associated with vascular dementia.
