Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI

Abstract

Spinal cord injury (SCI) is a debilitating condition currently lacking treatment. Severe SCI causes the loss of most supraspinal inputs and neuronal activity caudal to the injury, which, coupled with the limited endogenous capacity for spontaneous regeneration, can lead to complete functional loss even in anatomically incomplete lesions. We hypothesized that transplantation of mature dorsal root ganglia (DRG), genetically modified to express the NaChBac sodium channel, could serve as a therapeutic option for functionally complete SCI. We found that NaChBac expression increased the intrinsic excitability of DRG neurons, promoted cell survival and neurotrophic factor secretion in vitro. Transplantation of NaChBac-expressing dissociated DRGs improved voluntary locomotion seven weeks after injury compared to control groups. Animals transplanted with NaChBac-expressing DRGs also possessed higher tubulin-positive neuronal fiber and myelin preservation, although serotonergic descending fibers remained unaffected. We observed early preservation of the corticospinal tract fourteen days after injury and transplantation which was lost seven weeks after injury. Nevertheless, transplantation of NaChBac-expressing DRGs increased the neuronal excitatory input, by increased number of VGlut2 contacts, immediately caudal to the injuries. Our work suggests that the transplantation of NaChBac-expressing dissociated DRGs can rescue significant motor function retaining an excitatory neuronal relay activity immediately caudal to injury.