Despite recent progresses in robotic rehabilitation technologies, their efficacy for post-stroke motor recovery is still limited. Such limitations might stem from the insufficient enhancement of plasticity mechanisms, crucial for functional recovery. Here, we designed a clinically relevant strategy that combines robotic rehabilitation with chemogenetic stimulation of serotonin release to boost plasticity. These two approaches acted synergistically to enhance post-stroke motor performance. Indeed, mice treated with our combined therapy showed substantial functional gains that persisted beyond the treatment period and generalized to non-trained tasks. Motor recovery was associated with a reduction in electrophysiological and neuroanatomical markers of GABAergic neurotransmission, suggesting disinhibition in perilesional areas. To unveil the translational potentialities of our approach, we specifically targeted the serotonin 1A receptor by delivering Buspirone, a clinically approved drug, in stroke mice undergoing robotic rehabilitation. Administration of Buspirone restored motor impairments similarly to what observed with chemogenetic stimulation, showing the immediate translational potential of this combined approach to significantly improve motor recovery after stroke.

尽管机器人康复技术最近取得了进展，但它们对中风后运动恢复的功效仍然有限。这种限制可能源于对功能恢复至关重要的可塑性机制的增强不足。在这里，我们设计了一种临床相关策略，将机器人康复与血清素释放的化学遗传学刺激相结合，以提高可塑性。这两种方法协同作用以增强中风后的运动表现。事实上，用我们的联合疗法治疗的小鼠表现出显着的功能增益，这些增益持续超过治疗期，并推广到未经训练的任务。运动恢复与 GABA 能神经传递的电生理学和神经解剖学标志物的减少有关，表明病灶周围区域的去抑制作用。为了揭示我们方法的转化潜力，我们通过在接受机器人康复的中风小鼠中提供临床批准的药物丁螺环酮，专门针对血清素 1A 受体。丁螺环酮的给药恢复了与化学刺激所观察到的类似的运动障碍，显示了这种联合方法的直接转化潜力，可显着改善中风后的运动恢复。