Stroke survivors often suffer from severe motor impairments, highlighting the critical need for effective rehabilitation strategies. In experimental models, extensive task-specific motor training within the first few weeks post-stroke significantly mitigates motor deficits. However, whether more multimodal motor training approaches after stroke can restore task-specific performance in non-trained motor tasks remains largely unknown. Additionally, while stroke itself triggers structural brain reorganization, the influence of early multimodal motor training on this process remains unclear. Here, we employed T2-weighted MRI to investigate brain region-specific volumetric changes over eight weeks in rats subjected to stroke and subsequent early multimodal motor training. We found that this combination not only facilitated task-specific motor function recovery, but also induced dramatic, multi-region, brain-wide volumetric changes. Specifically, over 80 locations within 50 distinct brain regions across both hemispheres exhibited substantial volumetric alterations in a predominantly bilateral symmetric pattern. In contrast, stroke or training alone resulted in changes in 8-15 locations within 7-13 brain regions, with stroke alone primarily affecting the infarcted hemisphere. Analysis of temporal volume changes revealed two distinct trajectories in post-stroke trained rats: one of initial swelling followed by shrinkage, and another of initial shrinkage followed by swelling, suggesting an early and delayed motor learning period. Overall, our findings demonstrate that multimodal motor training early after stroke effectively restores task-specific motor function and profoundly reshapes brain structure on a brain-wide scale, offering vital insights for developing optimized rehabilitation protocols to maximize recovery in stroke patients.
