Multimodal rehabilitation promotes axonal sprouting and functional recovery in a murine model of spinal cord injury (SCI)

Spinal cord injury (SCI) is a devastating neurological disorder affecting millions of people worldwide, resulting in severe and permanent disabilities that significantly impact the individual's life. Rehabilitation is a commonly accepted and effective clinical treatment modality for neurological disabilities. A single form of rehabilitation training is, however, limited. Indeed, recent studies have reported that a combination of various training stra-tegies may be more promising in promoting functional recovery. However, few studies have focused on combining different forms of rehabilitative training. Here, we investigated the effect of combining treadmill training and single pellet grasping in a well-established model of murine SCI to assess whether combining rehabilitation approaches improve outcomes. In brief, one week following crush SCI, mice were subjected to the treadmill and single pellet grasping training (SPG) for a period of six weeks. Biotinylated dextran amine (BDA) was used to anterogradely trace corticospinal tract axons to assess functionally relevant axonal sprouting. Our results revealed that the combined training upregulated p-S6 expression, facilitated axonal sprouting, increased the formation of functional synaptic connections, and promoted functional recovery of the upper limb. Our study provides experimental evidence for the benefit of combining multiple modalities of rehabilitative strategies.