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Updated: Dec 15, 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
The brains of aged mice are characterized by altered tissue diffusion properties and cerebral microbleeds
Erik N Taylor1,2,3, Nasi Huang4,5, Jonathan Wisco6
1Department of Radiology, University of New Mexico, Albuquerque, NM, USA. eriktaylor@salud.unm.edu.
Background:
Brain aging is a major risk factor in the progression of cognitive diseases including Alzheimer's disease (AD) and vascular dementia. We investigated a mouse model of brain aging up to 24 months old (mo).
Methods:
A high field (11.7T) MRI protocol was developed to characterize specific features of brain aging including the presence of cerebral microbleeds (CMBs), morphology of grey and white matter, and tissue diffusion properties. Mice were selected from age categories of either young (3 mo), middle-aged (18 mo), or old (24 mo) and fed normal chow over the duration of the study. Mice were imaged in vivo with multimodal MRI, including conventional T2-weighted (T2W) and T2*-weighted (T2*W) imaging, followed by ex vivo diffusion-weighted imaging (DWI) and T2*W MR-microscopy to enhance the detection of microstructural features.
Results:
Structural changes observed in the mouse brain with aging included reduced cortical grey matter volume and enlargement of the brain ventricles. A remarkable age-related change in the brains was the development of CMBs found starting at 18 mo and increasing in total volume at 24 mo, primarily in the thalamus. CMBs presence was confirmed with high resolution ex vivo MRI and histology. DWI detected further brain tissue changes in the aged mice including reduced fractional anisotropy, increased radial diffusion, increased mean diffusion, and changes in the white matter fibers visualized by color-coded tractography, including around a large cortical CMB.
Conclusions:
The mouse is a valuable model of age-related vascular contributions to cognitive impairment and dementia (VCID). In composite, these methods and results reveal brain aging in older mice as a multifactorial process including CMBs and tissue diffusion alterations that can be well characterized by high field MRI.
Insights
Brain aging in mice shows reduced grey matter and enlarged ventricles. High-field MRI revealed age-related cerebral microbleeds and altered white matter diffusion, modeling vascular dementia.
Area of Science:
- Neuroscience
- Radiology
- Gerontology
Background:
- Brain aging is a key risk factor for cognitive decline, including Alzheimer's disease and vascular dementia.
- Investigated a mouse model to understand age-related brain changes up to 24 months old.
Purpose of the Study:
- Develop a high-field MRI protocol to characterize brain aging features.
- Assess cerebral microbleeds (CMBs), grey/white matter morphology, and diffusion properties in aging mice.
Main Methods:
- Utilized multimodal MRI (T2W, T2*W, DWI) in vivo and ex vivo on young (3 mo), middle-aged (18 mo), and old (24 mo) mice.
- Employed MR-microscopy for enhanced microstructural feature detection.
- Confirmed CMB presence with histology.
Main Results:
- Observed reduced cortical grey matter volume and enlarged ventricles with age.
- Detected CMBs starting at 18 months, increasing in volume by 24 months, primarily in the thalamus.
- DWI revealed decreased fractional anisotropy and increased diffusion in aged mice, with white matter tract changes.
Conclusions:
- The mouse model effectively represents age-related vascular contributions to cognitive impairment and dementia (VCID).
- High-field MRI can characterize multifactorial brain aging, including CMBs and diffusion alterations.
