Abstract
The growth of injured axons in the adult mammalian CNS is limited after injury. Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro. Transgenic or viral blockade of NgR function allows axonal sprouting in vivo. Here, we administered the soluble function-blocking NgR ectodomain [aa 27-310; NgR(310)ecto] to spinal-injured rats. Purified NgR(310)ecto-Fc protein was delivered intrathecally after midthoracic dorsal over-hemisection. Axonal sprouting of corticospinal and raphespinal fibers in NgR(310)ecto-Fc-treated animals correlates with improved spinal cord electrical conduction and improved locomotion. The ability of soluble NgR(310)ecto to promote axon growth and locomotor recovery demonstrates a therapeutic potential for NgR antagonism in traumatic spinal cord injury.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Axons / metabolism
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Axons / physiology*
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Evoked Potentials, Motor
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Female
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GPI-Linked Proteins
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Injections, Spinal
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Motor Activity
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Myelin Proteins / antagonists & inhibitors*
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Myelin-Associated Glycoprotein / antagonists & inhibitors*
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Myelin-Associated Glycoprotein / metabolism*
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Myelin-Oligodendrocyte Glycoprotein
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Nogo Proteins
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Nogo Receptor 1
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Oligodendroglia / metabolism
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Peptide Fragments / administration & dosage
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Peptide Fragments / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Cell Surface
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Receptors, Peptide / physiology*
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / pharmacology
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Serotonin / metabolism
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Solubility
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Spinal Cord / physiopathology
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Spinal Cord / ultrastructure
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Spinal Cord Injuries / metabolism
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Spinal Cord Injuries / pathology*
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Spinal Cord Injuries / physiopathology
Substances
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GPI-Linked Proteins
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Mog protein, rat
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Myelin Proteins
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Myelin-Associated Glycoprotein
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Myelin-Oligodendrocyte Glycoprotein
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NgR(310) Ecto-Fc protein
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Nogo Proteins
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Nogo Receptor 1
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Omg protein, rat
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Peptide Fragments
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Receptors, Cell Surface
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Receptors, Peptide
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Recombinant Fusion Proteins
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Rtn4 protein, rat
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Rtn4r protein, rat
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Serotonin