Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury. 2012

Philip Duffy, and Xingxing Wang, and Chad S Siegel, and Chad S Seigel, and Nathan Tu, and Mark Henkemeyer, and William B J Cafferty, and Stephen M Strittmatter
Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, CT 06536, USA.

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.

UI MeSH Term Description Entries
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009186 Myelin Sheath The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem. Myelin,Myelin Sheaths,Sheath, Myelin,Sheaths, Myelin
D009409 Nerve Crush Treatment of muscles and nerves under pressure as a result of crush injuries. Crush, Nerve
D009416 Nerve Regeneration Renewal or physiological repair of damaged nerve tissue. Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D009900 Optic Nerve The 2nd cranial nerve which conveys visual information from the RETINA to the brain. The nerve carries the axons of the RETINAL GANGLION CELLS which sort at the OPTIC CHIASM and continue via the OPTIC TRACTS to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the SUPERIOR COLLICULI and the SUPRACHIASMATIC NUCLEI. Though known as the second cranial nerve, it is considered part of the CENTRAL NERVOUS SYSTEM. Cranial Nerve II,Second Cranial Nerve,Nervus Opticus,Cranial Nerve, Second,Cranial Nerves, Second,Nerve, Optic,Nerve, Second Cranial,Nerves, Optic,Nerves, Second Cranial,Optic Nerves,Second Cranial Nerves
D011712 Pyramidal Tracts Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. Corticobulbar Tracts,Corticospinal Tracts,Decussation, Pyramidal,Corticobulbar Tract,Corticospinal Tract,Pyramidal Decussation,Pyramidal Tract,Tract, Corticobulbar,Tract, Corticospinal,Tract, Pyramidal,Tracts, Corticobulbar,Tracts, Corticospinal,Tracts, Pyramidal
D011903 Raphe Nuclei Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA. Caudal Linear Nucleus of the Raphe,Interfascicular Nucleus,Nucleus Incertus,Rostral Linear Nucleus of Raphe,Rostral Linear Nucleus of the Raphe,Superior Central Nucleus,Central Nucleus, Superior,Incertus, Nucleus,Nuclei, Raphe,Nucleus, Interfascicular,Nucleus, Raphe,Nucleus, Superior Central,Raphe Nucleus
D003902 Detergents Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. Cleansing Agents,Detergent Pods,Laundry Detergent Pods,Laundry Pods,Syndet,Synthetic Detergent,Agent, Cleansing,Agents, Cleansing,Cleansing Agent,Detergent,Detergent Pod,Detergent Pod, Laundry,Detergent Pods, Laundry,Detergent, Synthetic,Detergents, Synthetic,Laundry Detergent Pod,Laundry Pod,Pod, Detergent,Pod, Laundry,Pod, Laundry Detergent,Pods, Detergent,Pods, Laundry,Pods, Laundry Detergent,Synthetic Detergents
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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