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Cognitive deficits after focal cerebral ischemia in mice
1Departments of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
Background And Purpose:
The interpretation of cognitive data in many experimental stroke studies is problematic because middle cerebral artery occlusion (MCAO) is associated with sensorimotor alterations that may become confounding factors in cognitive testing. The purpose of the current study was to determine if it is possible to measure MCAO-induced cognitive deficits by using short durations of ischemia that do not result in alterations in sensorimotor behavior in mice.
Methods:
Male C57/Bl6 mice were subjected to 60 or 90 minutes of intraluminal MCAO or sham surgery. In the first cohort of animals (n=12/group), locomotor activity, balance, and coordination were evaluated 2 weeks after surgery. In a second cohort of animals (n=10/group), the effects of 60 minutes of MCAO on subsequent learning and memory were assessed with a step-down passive avoidance task beginning 1 week after surgery. In a third cohort of animals (n=8 to 10/group), training in a passive avoidance task was completed before 60 minutes of MCAO, then retention of the task was assessed 1 week after surgery. In all animals, infarction size was determined after 14 days of reperfusion with use of cresyl violet staining and quantitative image analysis.
Results:
There was no significant difference in infarction volume in the cerebral cortex or caudoputamen after 60 versus 90 minutes of MCAO. However, there was a significant increase in latency to move 1 body length in the 90-minute MCAO group compared with the 60-minute MCAO and sham groups. In 2 additional cohorts of animals, 60-minute MCAO was associated with a deficit in the acquisition and retention of a passive avoidance task regardless of whether the task training occurred before or after MCAO.
Conclusions:
Long-term cognitive deficits can be induced in mice by using a short duration of MCAO (60 minutes) that does not result in concomitant sensorimotor deficits.
Insights
Short middle cerebral artery occlusion (MCAO) in mice can induce cognitive deficits without sensorimotor impairments. This finding helps refine stroke models for cognitive research.
Area of Science:
- Neuroscience
- Stroke Research
- Animal Models
Background:
- Interpreting cognitive data in experimental stroke studies is challenging due to sensorimotor alterations from middle cerebral artery occlusion (MCAO).
- These sensorimotor changes can confound cognitive testing results.
Purpose of the Study:
- To determine if short MCAO durations can induce cognitive deficits without causing sensorimotor alterations in mice.
- To establish a refined animal model for studying stroke-related cognitive impairments.
Main Methods:
- Male C57/Bl6 mice underwent 60 or 90 minutes of MCAO or sham surgery.
- Sensorimotor function was assessed, followed by cognitive testing using a step-down passive avoidance task.
- Infarction size was quantified after reperfusion.
Main Results:
- No significant difference in infarction volume between 60 and 90 minutes of MCAO.
- A significant increase in movement latency was observed in the 90-minute MCAO group.
- 60-minute MCAO impaired both acquisition and retention of the passive avoidance task.
Conclusions:
- Short durations of MCAO (60 minutes) can induce cognitive deficits in mice.
- These deficits occur without significant sensorimotor impairments, offering a cleaner model for cognitive research.