Intermittent Skill Training Results in Moderate Improvement in Functional Outcome in a Mouse Model of Ischemic Stroke

Abstract

Background Stroke is a leading cause of disability worldwide. Focused training of the impaired limb has been shown to improve its functional outcome in animal models. However, most human stroke survivors exhibit persistent motor deficits, likely due to differences in rehabilitation intensity between experimental (animal) and clinical (human) settings. Objective The current study investigated the effect of training intensity on behavioral outcome in a mouse model of stroke. Methods Mice were trained preoperatively on a skilled reaching task. After training, mice received a unilateral photothrombotic stroke. Postoperatively, animals received either daily rehabilitative training (traditional intensity), intermittent rehabilitative training (every other day), or no rehabilitative training (control). Assessment of the impaired limb occurred after 14 training sessions (14 days for the Traditional group; 28 days for the Intermittent group). Results Assessment of the impaired limb illustrated that traditional, daily training resulted in significantly better performance than no training, while intermittent training offered moderate performance gains. Mice receiving intermittent training performed significantly better than control mice but did not exhibit reaching performance as strong as that of animals trained daily. Conclusions The intensity of rehabilitation is important for optimal recovery. Although intermediate intensity offers some benefit, it is not intensive enough to mimic the performance gains traditionally observed in animal models. These results suggest that intensive training, which is often unavailable for human stroke survivors, is necessary to achieve an optimal functional outcome. The lower bounds of training intensity for functional benefit still need to be determined.