Cognitive deficits after focal cerebral ischemia in mice

Background and Purpose-The interpretation of cognitive data in many experim ental stroke studies is problematic because middle cerebral artery occlusio n (MCAO) is associated with sensorimotor alterations that may become confou nding 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 sens orimotor behavior in mice. Methods-Male C57/B16 mice were subjected to 60 or 90 minutes of intralumina l MCAO or sham surgery. In the first cohort of animals (n=12/group), locomo tor activity, balance, and coordination were evaluated 2 weeks after surger y. In a second cohort of animals (n= 10/group), the effects of 60 minutes o f MCAO on subsequent learning and memory were assessed with a step-down pas sive avoidance task beginning 1 week after surgery. In a third cohort of an imals (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 a nalysis. Results-There was no significant difference in infarction volume in the cer ebral cortex or caudoputamen after 60 versus 90 minutes of MCAO. However, t here 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 ad ditional cohorts of animals, 60-minute MCAO was associated with a deficit i n the acquisition and retention of a passive avoidance task regardless of w hether 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 sen sorimotor deficits.