title: A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury.
abstract: Descending propriospinal neurons (DPSN) are known to establish functional relays for supraspinal signals, and they display a greater growth response after injury than do the long projecting axons. However, their regenerative response is still deficient due to their failure to depart from growth supportive cellular transplants back into the host spinal cord, which contains numerous impediments to axon growth. Here we report the construction of a continuous growth-promoting pathway in adult rats, formed by grafted Schwann cells overexpressing glial cell line-derived neurotrophic factor (GDNF). We demonstrate that such a growth-promoting pathway, extending from the axonal cut ends to the site of innervation in the distal spinal cord, promoted regeneration of DPSN axons through and beyond the lesion gap of a spinal cord hemisection. Within the distal host spinal cord, regenerated DPSN axons formed synapses with host neurons leading to the restoration of action potentials and partial recovery of function.
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, and Department of Neurological Surgery, Goodman and Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Ling-Xiao
authors.initials: LX
authors.lastname: Deng
authors.forename: Ping
authors.initials: P
authors.lastname: Deng
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Ruan
authors.forename: Zao Cheng
authors.initials: ZC
authors.lastname: Xu
authors.forename: Nai-Kui
authors.initials: NK
authors.lastname: Liu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wen
authors.forename: George M
authors.initials: GM
authors.lastname: Smith
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives; D002452:Cell Count; D003911:Dextrans; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016557:Guided Tissue Regeneration, Periodontal; D066298:In Vitro Techniques; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D018993:Myelin P0 Protein / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology* / Q000637:transplantation*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery*; D013266:Stilbamidines; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D003911:Dextrans; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D018993:Myelin P0 Protein; D013266:Stilbamidines; D016708:Synaptophysin; C569016:Syp protein, rat; C076397:biotinylated dextran amine; D049452:Green Fluorescent Proteins; D001710:Biotin
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