Related Experiment Video
Updated: May 10, 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
Six-month ischemic mice show sensorimotor and cognitive deficits associated with brain atrophy and axonal
Elisa R Zanier1, Francesca Pischiutta, Pia Villa
1IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, Milan, Italy.
Aims:
To identify long-term sensorimotor and cognitive deficits and to evaluate structural alterations in brain ischemic mice.
Methods:
C57Bl/6J male mice were subjected to 30 min transient middle cerebral artery occlusion (tMCAo) or sham surgery. Sensorimotor deficits, exploratory behavior, and cognitive functions were evaluated up to 6 months. Cortical and subcortical damage were analyzed by MRI multiparameter analysis and histopathology.
Results:
tMCAo mice showed significant sensorimotor deficits in the rotarod, negative geotaxis, neuroscore, and beam walk tests. They also showed impairment in exploratory behavior in the open field test and in spatial learning in the Morris water maze. T2-weighted MRI revealed a volume reduction in injured brain areas at 12 and 24 weeks postinjury. Brain atrophy was shown by MRI and conventional postmortem analysis. Diffusion tensor imaging on the external capsule showed increased values of axial and radial diffusivity. Fiber tracking revealed a reduction in the number and length of ipsilateral fibers.
Conclusions:
tMCAo in mice induces sensorimotor and cognitive impairments detectable at least up to 6 months postinjury, associated with brain atrophy, and axonal and myelin damage of the external capsule. These behavioral tests and anatomical investigations may represent important tools in translational studies in cerebral ischemia.
Insights
Transient middle cerebral artery occlusion (tMCAo) in mice causes lasting sensorimotor and cognitive deficits. This study reveals long-term brain atrophy and axonal damage following stroke in these models.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Animal Models of Stroke
Background:
- Stroke is a leading cause of long-term disability.
- Understanding the chronic effects of ischemic stroke is crucial for developing effective therapies.
- Animal models are essential for studying stroke pathophysiology and testing interventions.
Purpose of the Study:
- To investigate long-term sensorimotor and cognitive deficits after transient middle cerebral artery occlusion (tMCAo) in mice.
- To evaluate structural brain alterations using advanced imaging techniques.
- To establish a reliable preclinical model for studying chronic stroke effects.
Main Methods:
- Male C57Bl/6J mice underwent 30-minute tMCAo or sham surgery.
- Behavioral assessments included sensorimotor tests (rotarod, beam walk), exploratory behavior (open field), and spatial learning (Morris water maze) up to 6 months post-stroke.
- Brain structural integrity was analyzed using multiparameter MRI and histopathology.
Main Results:
- tMCAo mice exhibited persistent sensorimotor and cognitive impairments.
- MRI revealed significant brain atrophy and volume reduction in injured areas.
- Diffusion tensor imaging showed increased diffusivity and reduced axonal integrity in the external capsule.
Conclusions:
- tMCAo in mice induces long-lasting sensorimotor and cognitive deficits.
- Structural damage, including brain atrophy and axonal/myelin damage, correlates with functional impairments.
- This model provides valuable insights for translational stroke research.
