Abstract W P99: A Time Window of Heightened Plasticity to Training After Ischemic Stroke in the Mouse is Extended By Fluoxetine if Provided Within the First Week After Stroke

Abstract

Background: and purpose - Data in humans and in non-human animal models suggest that most recovery from motor impairment occurs in the first 4 weeks after stroke and is mediated in part by increased responsiveness to training in this short time period. We tested the hypothesis that there is a gradient of diminishing responsiveness to training in the first week after stroke in the mouse. We then tested whether fluoxetine can extend the time window over which large training-related gains can be expected. Methods: Adult C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke or sham stroke in the caudal forelimb area (CFA can be considered rodent primary motor cortex). The mice were then retrained after a 1- or 7-day delay in the presence or absence of fluoxetine injected IP daily beginning after a 1- or 7-day delay. Results: Training-associated recovery of prehension was complete if training was initiated after a 1-day delay but incomplete if training was initiated after a 7-day delay, even with additional training days. Daily fluoxetine administration after stroke was associated with complete recovery of prehension even if training was delayed 7 days but only if fluoxetine was administered beginning 1 day but not 7 days after stroke. Conclusions: We conclude that there is a sensitive period 7 days after stroke during which motor training is more likely to promote recovery and that this period can be extended by fluoxetine only if administration begins during the first week after stroke. Our mouse model, with all of the attendant genetic benefits, may allow us to determine at the cellular and molecular level how behavioral training and endogenous plasticity interact to mediate recovery.