Enriched Rehabilitation Reduces Abnormal Motor Synergies and Enhances Motor Plasticity Following Severe Stroke in Rats.

Abstract

Stroke results in loss of upper motor neuron control over voluntary movements and emergence of abnormal synergies. Presently, it is unclear to what extent poststroke recovery reflects true recovery (restitution), compensation, or some combination of these processes. Here, we investigated this question using behavioral and kinematic analyses of skilled reaching in rats subjected to severe stroke that affected both the forelimb motor cortex and dorsolateral striatum. After stroke, male rats either spontaneously recovered or received enriched rehabilitation. We assessed forelimb motor recovery using behavioral and kinematic outcome measures. To provide insights into the mechanisms underlying the effects of rehabilitation on behavior, we used intracortical microstimulation and FosB (protein fosB) immunostaining techniques. Enriched rehabilitation significantly improved food pellet retrieval in the staircase-reaching task. Rehabilitation resulted in several poststroke flexion synergies returning to prestroke patterns, and across subjects, these changes correlated with the intensity of rehabilitation. Enriched rehabilitation increased the proportion of distal movement representation in the perilesional cortex and increased use-dependent activation in the ipsilesional red nucleus. These results provide evidence that enriched rehabilitation enhances recovery, at least in part, by restitution of forelimb function following severe stroke. Furthermore, the restitution of function is associated with changes in multiple motor-related structures at different levels of the central nervous system. A better understanding of the processes that underlie improved motor performance, along with the identification of midbrain circuits activated by rehabilitation, represent new insights and potential targets for optimizing poststroke recovery.