Related Experiment Video
Updated: Jul 25, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
The behavioural effect of middle cerebral artery occlusion on apolipoprotein-E deficient mice
J P Hatcher1, D Virley, S J Hadingham
1Neurology CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK. jon_hatcher-1@gsk.com
Abstract:
The behavioural effects of middle cerebral artery occlusion (MCAO) in apolipoprotein-E deficient (Apo-E KO) mice were investigated using a modified SHIRPA protocol and compared with effects in wild type littermate controls. The MCA was permanently occluded by insertion of an intraluminal filament to its origin on the Circle of Willis and behavioural responses were observed 24 h later. MCAO treatment caused a range of changes in the wild type mice whereas, few differences were observed in the Apo-E KO mice in the behavioural observation. In the rotarod task, MCAO operated wild type mice showed a significant reduction in performance compared with sham-operated and non-operated animals. In contrast, both sham and MCAO operated Apo-E KO mice showed significant impairment compared with non-operated controls. A significant reduction in performance was also observed in sham-operated Apo-E KO compared with sham-operated wild type mice. In locomotor activity tests, no significant reduction in activity was observed between non-operated and sham-operated wild type controls, whereas a significant reduction was found between sham operated and MCAO operated mice. In the Apo-E KO mice, both sham and MCAO-operated animals showed a reduction in locomotor activity compared with non-operated mice. Furthermore, Apo-E KO MCAO mice showed a worsened deficit in locomotor activity, which was significantly correlated with exacerbated cortical lesion volume, unlike wild-type MCAO mice. This study shows that Apo-E KO animals demonstrate an impaired functional recovery post surgery which may be further compounded by post experimental stroke and also demonstrates the utility of the SHIRPA test system for investigating behavioural changes in functional outcome post stroke.
Insights
Apolipoprotein-E deficient (Apo-E KO) mice show impaired functional recovery after middle cerebral artery occlusion (MCAO) stroke surgery. These Apo-E KO mice exhibit worsened motor deficits and greater lesion volumes post-stroke compared to wild-type controls.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Genetics
Background:
- Stroke is a leading cause of disability, and understanding its effects on different genetic backgrounds is crucial.
- Apolipoprotein-E deficiency (Apo-E KO) is linked to cardiovascular issues and may influence stroke outcomes.
- Investigating behavioral changes post-stroke in Apo-E KO mice can reveal mechanisms of functional recovery.
Purpose of the Study:
- To investigate the behavioral effects of middle cerebral artery occlusion (MCAO) in apolipoprotein-E deficient (Apo-E KO) mice.
- To compare the functional recovery of Apo-E KO mice with wild-type littermate controls after experimental stroke.
- To assess the utility of the modified SHIRPA protocol in evaluating behavioral changes post-stroke.
Main Methods:
- Middle cerebral artery occlusion (MCAO) was induced using an intraluminal filament in Apo-E KO and wild-type mice.
- Behavioral responses were assessed 24 hours post-surgery using a modified SHIRPA protocol.
- Performance was evaluated using rotarod tasks and locomotor activity tests.
Main Results:
- MCAO caused significant motor deficits in wild-type mice, while Apo-E KO mice showed impairments even after sham surgery.
- Both sham and MCAO-operated Apo-E KO mice exhibited reduced locomotor activity compared to non-operated controls.
- Apo-E KO mice subjected to MCAO showed worsened locomotor deficits correlated with larger cortical lesion volumes compared to wild-type MCAO mice.
Conclusions:
- Apo-E KO mice demonstrate impaired functional recovery following experimental stroke.
- The surgical procedure itself significantly impacts the behavior of Apo-E KO mice, suggesting compromised resilience.
- The SHIRPA test system is effective for assessing behavioral outcomes and functional recovery after stroke in mouse models.
