title: Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury.
abstract: Recovery of neurological function after traumatic injury of the adult mammalian central nervous system is limited by lack of axonal growth. Myelin-derived inhibitors contribute to axonal growth restriction, with ephrinB3 being a developmentally important axonal guidance cue whose expression in mature oligodendrocytes suggests a role in regeneration. Here we explored the in vivo regeneration role of ephrinB3 using mice lacking a functional ephrinB3 gene. We confirm that ephrinB3 accounts for a substantial portion of detergent-resistant myelin-derived inhibition in vitro. To assess in vivo regeneration, we crushed the optic nerve and examined retinal ganglion fibers extending past the crush site. Significantly increased axonal regeneration is detected in ephrinB3(-/-) mice. Studies of spinal cord injury in ephrinB3(-/-) mice must take into account altered spinal cord development and an abnormal hopping gait before injury. In a near-total thoracic transection model, ephrinB3(-/-) mice show greater spasticity than wild-type mice for 2 mo, with slightly greater hindlimb function at later time points, but no evidence for axonal regeneration. After a dorsal hemisection injury, increased corticospinal and raphespinal growth in the caudal spinal cord are detected by 6 wk. This increased axonal growth is accompanied by improved locomotor performance measured in the open field and by kinematic analysis. Thus, ephrinB3 contributes to myelin-derived axonal growth inhibition and limits recovery from adult CNS trauma.
authors.affiliation: Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Duffy
authors.forename: Xingxing
authors.initials: X
authors.lastname: Wang
authors.forename: Chad S
authors.initials: CS
authors.lastname: Siegel
authors.forename: Chad S
authors.initials: CS
authors.lastname: Seigel
authors.forename: Nathan
authors.initials: N
authors.lastname: Tu
authors.forename: Mark
authors.initials: M
authors.lastname: Henkemeyer
authors.forename: William B J
authors.initials: WB
authors.lastname: Cafferty
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003902:Detergents / Q000494:pharmacology; D036389:Ephrin-B3 / Q000172:deficiency / Q000378:metabolism*; D017353:Gene Deletion; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011903:Raphe Nuclei / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery
chemical_list: D003902:Detergents; D036389:Ephrin-B3