Exploration on neurobiological mechanisms of the central–peripheral–central closed-loop rehabilitation

Central and peripheral interventions for brain injury rehabilitation have been widely employed. However, as patients' requirements and expectations for stroke rehabilitation have gradually increased, the limitations of simple central intervention or peripheral intervention in the rehabilitation application of stroke patients' function have gradually emerged. Studies have suggested that central intervention promotes the activation of functional brain regions and improves neural plasticity, whereas peripheral intervention enhances the positive feedback and input of sensory and motor control modes to the central nervous system, thereby promoting the remodeling of brain function. Based on the model of a central-peripheral-central (CPC) closed loop, the integration of center and peripheral interventions was effectively completed to form "closed-loop" information feedback, which could be applied to specific brain areas or function-related brain regions of patients. Notably, the closed loop can also be extended to central and peripheral immune systems as well as central and peripheral organs such as the brain-gut axis and lung-brain axis. In this review article, the model of CPC closed-loop rehabilitation and the potential neuroimmunological mechanisms of a closed-loop approach will be discussed. Further, we highlight critical questions about the neuroimmunological aspects of the closed-loop technique that merit future research attention.