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Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice
Published on: October 20, 2016
Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse
Valentine Bouët1, Thomas Freret, Jérôme Toutain
1UMR 6185 - CNRS, Neurodegenerescence: models and therapeutic strategies, University of Caen Basse-Normandie, CYCERON, Bd H Becquerel - BP 5229, F-14074 Caen Cedex, France. bouet@cyceron.fr
Abstract:
Whereas behavioral impairments after stroke are increasingly studied in the rat, little is known about the long-term functional consequences of focal ischemia in the mouse. To address this issue, Swiss mice underwent transient (60 min) intraluminal occlusion of the middle cerebral artery (MCAo) or sham surgery. Sensorimotor (chimney, accelerating rotarod, pole, corner, adhesive removal and staircase tests) and cognitive (passive avoidance and Morris water maze) performances were regularly assessed during 1 month, after which the final histological lesion was measured. Motor coordination and balance, assessed by the chimney and rotarod tests, were transiently altered by MCAo. Moreover, bradykinesia was evidenced by the pole test. The most striking and long-lasting (1 month) sensorimotor deficits were postural asymmetries on the corner test, bilateral skilled forepaw reaching deficits on the staircase test and a contralateral sensorimotor impairment on the adhesive removal test. MCAo animals showed normal spatial learning abilities on the Morris water maze test, but they displayed learning deficits measured by the passive avoidance test. This latter deficit was significantly correlated with both cortical and striatal damage. Our findings demonstrate the usefulness of three tests that had never been reported in the mouse after ischemia: the adhesive removal, staircase and pole tests, which showed deficits 1 month after ischemia and should therefore constitute meaningful tools in mice for assessing both neuroprotective and regenerative therapies in stroke preclinical studies.
Insights
This study investigated long-term functional deficits in mice after middle cerebral artery occlusion (MCAo) stroke. Novel adhesive removal, staircase, and pole tests revealed persistent sensorimotor impairments, useful for stroke therapy evaluation.
Area of Science:
- Neuroscience
- Neurology
- Stroke Research
Background:
- Stroke research predominantly uses rats, with limited understanding of long-term mouse functional consequences after focal ischemia.
- Focal cerebral ischemia models are crucial for studying stroke pathophysiology and evaluating therapeutic interventions.
Purpose of the Study:
- To characterize long-term sensorimotor and cognitive deficits in mice following transient middle cerebral artery occlusion (MCAo).
- To identify novel behavioral tests for assessing stroke-induced impairments in mice.
Main Methods:
- Swiss mice underwent transient (60 min) MCAo or sham surgery.
- A battery of sensorimotor (chimney, rotarod, pole, corner, adhesive removal, staircase) and cognitive (passive avoidance, Morris water maze) tests were performed for 1 month post-MCAo.
- Histological analysis quantified lesion volume.
Main Results:
- MCAo induced transient motor coordination and balance deficits (chimney, rotarod) and bradykinesia (pole test).
- Persistent sensorimotor deficits included postural asymmetry (corner test), skilled forepaw reaching impairment (staircase test), and contralateral sensorimotor deficits (adhesive removal test).
- Spatial learning remained intact (Morris water maze), but passive avoidance learning was impaired, correlating with cortical and striatal damage.
Conclusions:
- The adhesive removal, staircase, and pole tests are valuable tools for detecting long-lasting behavioral deficits in mice post-ischemia.
- These tests demonstrate significant sensorimotor impairments one month after MCAo.
- The identified tests are recommended for preclinical evaluation of neuroprotective and regenerative therapies for stroke.
