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000269434 1001_ $$aHingorani, Sonia$$b0
000269434 245__ $$aTransplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI
000269434 260__ $$aNew York, NY$$bNature Publ. Group$$c2024
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000269434 520__ $$aSpinal cord injury (SCI) is a debilitating condition currently lacking treatment. Severe SCI causes the loss of most supraspinal inputs and neuronal activity caudal to the injury, which, coupled with the limited endogenous capacity for spontaneous regeneration, can lead to complete functional loss even in anatomically incomplete lesions. We hypothesized that transplantation of mature dorsal root ganglia (DRGs) genetically modified to express the NaChBac sodium channel could serve as a therapeutic option for functionally complete SCI. We found that NaChBac expression increased the intrinsic excitability of DRG neurons and promoted cell survival and neurotrophic factor secretion in vitro. Transplantation of NaChBac-expressing dissociated DRGs improved voluntary locomotion 7 weeks after injury compared to control groups. Animals transplanted with NaChBac-expressing DRGs also possessed higher tubulin-positive neuronal fiber and myelin preservation, although serotonergic descending fibers remained unaffected. We observed early preservation of the corticospinal tract 14 days after injury and transplantation, which was lost 7 weeks after injury. Nevertheless, transplantation of NaChBac-expressing DRGs increased the neuronal excitatory input by an increased number of VGLUT2 contacts immediately caudal to the injury. Our work suggests that the transplantation of NaChBac-expressing dissociated DRGs can rescue significant motor function, retaining an excitatory neuronal relay activity immediately caudal to injury.
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000269434 650_7 $$2Other$$adorsal root ganglia
000269434 650_7 $$2Other$$afunctional recovery
000269434 650_7 $$2Other$$ainhibitory and excitatory input
000269434 650_7 $$2Other$$aneuronal survival
000269434 650_7 $$2Other$$aneuronal transplantation
000269434 650_7 $$2Other$$asodium channel
000269434 650_7 $$2Other$$aspinal cord injury
000269434 650_7 $$2NLM Chemicals$$aSodium Channels
000269434 650_2 $$2MeSH$$aGanglia, Spinal: metabolism
000269434 650_2 $$2MeSH$$aAnimals
000269434 650_2 $$2MeSH$$aSpinal Cord Injuries: metabolism
000269434 650_2 $$2MeSH$$aSpinal Cord Injuries: therapy
000269434 650_2 $$2MeSH$$aSpinal Cord Injuries: genetics
000269434 650_2 $$2MeSH$$aLocomotion
000269434 650_2 $$2MeSH$$aSodium Channels: metabolism
000269434 650_2 $$2MeSH$$aSodium Channels: genetics
000269434 650_2 $$2MeSH$$aRats
000269434 650_2 $$2MeSH$$aFemale
000269434 650_2 $$2MeSH$$aRecovery of Function
000269434 650_2 $$2MeSH$$aDisease Models, Animal
000269434 650_2 $$2MeSH$$aNeurons: metabolism
000269434 650_2 $$2MeSH$$aMice
000269434 650_2 $$2MeSH$$aGene Expression
000269434 650_2 $$2MeSH$$aMyelin Sheath: metabolism
000269434 650_2 $$2MeSH$$aCell Survival
000269434 7001_ $$aPaniagua Soriano, Guillem$$b1
000269434 7001_ $$aSánchez Huertas, Carlos$$b2
000269434 7001_ $$aVillalba Riquelme, Eva María$$b3
000269434 7001_ $$aLópez Mocholi, Eric$$b4
000269434 7001_ $$aMartínez Rojas, Beatriz$$b5
000269434 7001_ $$aAlastrué Agudo, Ana$$b6
000269434 7001_ $$0P:(DE-2719)2810386$$aDupraz, Sebastián$$b7$$udzne
000269434 7001_ $$aFerrer Montiel, Antonio Vicente$$b8
000269434 7001_ $$00000-0002-6035-9491$$aMoreno Manzano, Victoria$$b9
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