title: Antisense vimentin cDNA combined with chondroitinase ABC promotes axon regeneration and functional recovery following spinal cord injury in rats.
abstract: The formation of glial scar restricts axon regeneration after spinal cord injury (SCI) in adult mammalian. Chondroitin sulfate proteoglycans (CSPGs) are mostly secreted by reactive astrocytes, which form dense scar tissues after SCI. Chondroitinase ABC (ChABC), which can digest CSPGs, is a promising therapeutic strategy for SCI. However, to date ChABC has exhibited only limited success in the treatment of chronic SCI. The intermediate filament protein vimentin underpins the cytoskeleton of reactive astrocytes. We targeted glial scar in injured spinal cord by sustained infusion of ChABC and antisense vimentin cDNA. Using anterograde tracing, BBB scoring and hind limb placing response, we found that this combined treatment promoted axon regeneration and functional recovery after SCI in rats. Our results indicate that axon regeneration may be promoted by modified physical and biochemical characteristics of intra- and extracellular architecture in glial scar tissues. Theses findings could potentially help us to understand better the composition of glial scar in central nervous system injury.
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Yongzhi
authors: Y
authors: Xia
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Yi
authors: Y
authors: Yan
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Haijian
authors: H
authors: Xia
authors: Department of Neurosurgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors: Tianzhi
authors: T
authors: Zhao
authors: Department of Neurosurgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors: Weihua
authors: W
authors: Chu
authors: Department of Neurosurgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors: Shengli
authors: S
authors: Hu
authors: Department of Neurosurgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors: Hua
authors: H
authors: Feng
authors: Department of Neurosurgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China. Electronic address: jklin_tmmu@163.com.
authors: Jiangkai
authors: J
authors: Lin
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D019765:Chondroitin ABC Lyase / Q000494:pharmacology* / Q000627:therapeutic use; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D016373:DNA, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D018076:DNA, Complementary / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D011712:Pyramidal Tracts / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014746:Vimentin / Q000235:genetics*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D016373:DNA, Antisense; D018076:DNA, Complementary; D014746:Vimentin; D019765:Chondroitin ABC Lyase
keywords: Axon regeneration; Chondroitinase ABC; Glial fibrillary acidic protein; Glial scar; Spinal cord injury; Vimentin