The critical role of cerebrospinal fluid-contacting neurons in spinal cord injury repair mediated by treadmill training

Adult neural stem cells play a significant role in promoting motor function recovery after spinal cord injury (SCI) through rehabilitative exercise. However, it remains unclear whether cerebrospinal fluid-contacting neurons (CSF-cNs), which possess the potential to act as neural stem cells, are involved in treadmill training-facilitated SCI repair. This study aimed to investigate the role of CSF-cNs in this process. Treadmill training was performed on female C57BL/6 mice with SCI to assess the activation and proliferation of CSF-cNs with neural stem cell potential. The effects of treadmill training on axonal growth, myelin regeneration, tissue repair, and motor function recovery were evaluated. To further validate the role of CSF-cNs in exercise-induced spinal cord repair, Pkd2l1 −/− mice exhibiting CSF-cNs depletion underwent treadmill training after SCI, and the resulting changes in neural stem cell proliferation and spinal cord repair were assessed. Treadmill training activated the neural stem cell potential of CSF-cNs, promoted their proliferation, and was accompanied by enhanced axon growth, myelin regeneration, and motor function recovery. In contrast, a significant reduction in proliferating cells around the central canal of the spinal cord was observed in Pkd2l1 −/− mice. Furthermore, deletion of Pkd2l1 significantly attenuated the beneficial effects of treadmill training on motor function recovery in SCI mice. CSF-cNs play a critical role in SCI recovery enhanced by treadmill training. These findings highlight the potential of CSF-cNs as a therapeutic target for the development of novel strategies to treat SCI.