A Critical Threshold of Rehabilitation Involving Brain-Derived Neurotrophic Factor Is Required for Poststroke Recovery

Abstract

Background. Enriched rehabilitation (ER; environmental enrichment plus skilled reaching) improves recovery after middle cerebral artery occlusion (MCAo) in rats. Fundamental issues such as whether ER is effective in other models, optimal rehabilitation intensity, and underlying recovery mechanisms have not been fully assessed. Objective. The authors tested whether the efficacy of ER varies with ischemia model and assessed the importance of rehabilitation intensity and brain-derived neurotrophic factor (BDNF) in recovery. Methods. Rats in experiment 1 received 8 weeks of ER or remained in standard housing. Functional outcome was assessed with the staircase and cylinder tasks. Surprisingly, ER provided no functional benefit in any model. In this experiment, ER was delivered during the light phase, whereas other studies delivered ER in the dark phase of the light cycle. It was hypothesized that in the light, rats engaged in less rehabilitation or alternatively that BDNF was lower. Experiment 2 tested these hypotheses. Following MCAo, rats received ER in either the light or dark phase of the light cycle. Functional outcome was assessed and BDNF levels were measured in the motor cortex and hippocampus. Results. Recovery was accompanied by increased BDNF. This occurred only in rats that received ER in the dark and these animals reached more than those in the light condition. Conclusions. Data suggest that there is a critical threshold of rehabilitation, below which recovery will not occur, and that BDNF mediates functional recovery. The use of intensive rehabilitation therapies for stroke patients is strongly supported.