Long-term deficits of the paretic limb follow post-stroke compensatory limb use in C57BL/6 mice

• Nonparetic limb training in the mouse functions as a model of compensatory limb use.
• Fifteen days of early nonparetic limb training in the mouse results in long-term deficits of the paretic limb.
• Twenty-eight days of rehabilitative training after early nonparetic limb training does not improve skilled reaching.

Stroke is a leading cause of long-term disability that most often results in impairment of a single limb, contralateral to the injury (paretic limb). While stroke survivors often receive some type of rehabilitative training, chronic deficits persist. It has been suggested that compensatory use of the nonparetic limb immediately after injury may underlie these long-term consequences. The current study investigated the behavioral effects of early compensatory limb use on behavioral outcome of the paretic limb in a mouse model of stroke. Mice received unilateral stroke after acquiring skilled motor performance on a reaching task. Following injury, mice received either delayed rehabilitation of the paretic limb or compensatory limb training prior to delayed rehabilitative training. After 28 days of focused rehabilitative training of the paretic limb, mice that had previously received compensatory limb training exhibited performance that was similar to their initial deficit after stroke while mice that received delayed rehabilitative training improved to pre-operative performance levels. Our results indicate that even with extensive focused training of the paretic limb, early compensatory limb use has a lasting impact on the behavioral flexibility and ultimate functional outcome of the paretic limb.