PDF(Pubmed)
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 (DRGs) 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 and promoted cell survival and neurotrophic factor secretion in vitro. Transplantation of NaChBac-expressing dissociated DRGs improved voluntary locomotion 7 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 14 days after injury and transplantation, which was lost 7 weeks after injury. Nevertheless, transplantation of NaChBac-expressing DRGs increased the neuronal excitatory input by an increased number of VGLUT2 contacts immediately caudal to the injury. 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.
摘要：
脊髓损伤（SCI）是一种目前缺乏治疗的衰弱状况。严重的脊髓损伤会导致脊髓上大部分输入和损伤后神经元活动的丧失，which,再加上自发再生的内源性能力有限，即使在解剖学上不完整的病变中，也会导致功能完全丧失。我们假设成熟背根神经节（DRG）的移植，转基因表达NaChBac钠通道，可以作为功能完全SCI的治疗选择。我们发现NaChBac表达增加了DRG神经元的内在兴奋性，在体外促进细胞存活和神经营养因子分泌。与对照组相比，表达NaChBac的解离DRG的移植改善了损伤后7周的自愿运动。移植有NaChBac表达DRGs的动物还具有较高的微管蛋白阳性神经元纤维和髓鞘保存，尽管血清素能下降纤维未受影响。我们观察到损伤和移植后14天皮质脊髓束的早期保存，而损伤后7周丢失。然而，表达NaChBac的DRGs的移植增加了神经元兴奋性输入，通过增加VGlut2触点的数量，立即尾随受伤。我们的工作表明，表达NaChBac的解离DRGs的移植可以挽救重要的运动功能，并在损伤后立即保留兴奋性神经元中继活动。
