Very Early Initiation Reduces Benefits of Poststroke Rehabilitation Despite Increased Corticospinal Projections

Background. Although the effect of rehabilitation is influenced by aspects of the training protocol, such as initiation time and intensity of training, it is unclear whether training protocol modifications affect the corticospinal projections. Objective. The present study was designed to investigate how modification of initiation time (time-dependency) and affected forelimb use (use-dependency) influence the effects of rehabilitation on functional recovery and corticospinal projections. Methods. The time-dependency of rehabilitation was investigated in rats forced to use their impaired forelimb immediately, at 1 day, and 4 days after photothrombotic stroke. The use-dependency of rehabilitation was investigated by comparing rats with affected forelimb immobilization (forced nonuse), unaffected forelimb immobilization (forced use), and a combination of forced use and skilled forelimb training beginning at 4 days after stroke. Results. Although forced use beginning 1 day or 4 days after stroke caused significant functional improvement, immediate forced limb use caused no functional improvement. On the other hand, a combination of forced use and skilled forelimb training boosted functional recovery in multiple tasks compared to simple forced use treatment. Histological examination showed that no treatment caused brain damage. However, a retrograde tracer study revealed that immediate forced use and combination training, including forced use and skilled forelimb training, increased corticospinal projections from the contralesional and ipsilesional motor cortex, respectively. Conclusions. These results indicate that although both very early initiation time and enhanced skilled forelimb use increased corticospinal projections, premature initiation time hampers the functional improvement induced by poststroke rehabilitation.