title: Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation.
abstract: Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4-/- mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.
authors: 1] Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, TWIns, Waseda University, Tokyo, 162-8480 Japan [2] Research Fellow of Japan Society for the Promotion of Science.
authors: Jun
authors: J
authors: Nagai
authors: Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, TWIns, Waseda University, Tokyo, 162-8480 Japan.
authors: Yoshiteru
authors: Y
authors: Kitamura
authors: Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, TWIns, Waseda University, Tokyo, 162-8480 Japan.
authors: Kazuki
authors: K
authors: Owada
authors: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.
authors: Naoya
authors: N
authors: Yamashita
authors: Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, 236-0004, Japan.
authors: Kohtaro
authors: K
authors: Takei
authors: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.
authors: Yoshio
authors: Y
authors: Goshima
authors: Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, TWIns, Waseda University, Tokyo, 162-8480 Japan.
authors: Toshio
authors: T
authors: Ohshima
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001369:Axons / Q000378:metabolism; D002921:Cicatrix / Q000235:genetics* / Q000473:pathology*; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D017353:Gene Deletion; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D009043:Motor Activity; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology*
chemical_list: C526904:Dpysl3 protein, mouse; D009419:Nerve Tissue Proteins
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