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      Delayed Systemic Nogo-66 Receptor Antagonist Promotes Recovery from Spinal Cord Injury

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          Abstract

          Traumatized axons possess an extremely limited ability to regenerate within the adult mammalian CNS. The myelin-derived axon outgrowth inhibitors Nogo, oligodendrocyte-myelin glycoprotein, and myelin-associated glycoprotein, all bind to an axonal Nogo-66 receptor (NgR) and at least partially account for this lack of CNS repair. Although the intrathecal application of an NgR competitive antagonist at the time of spinal cord hemisection induces significant regeneration of corticospinal axons, such immediate local therapy may not be as clinically feasible for cases of spinal cord injury. Here, we consider whether this approach can be adapted to systemic therapy in a postinjury therapeutic time window. Subcutaneous treatment with the NgR antagonist peptide NEP1–40 (Nogo extracellular peptide, residues 1–40) results in extensive growth of corticospinal axons, sprouting of serotonergic fibers, upregulation of axonal growth protein SPRR1A (small proline-rich repeat protein 1A), and synapse re-formation. Locomotor recovery after thoracic spinal cord injury is enhanced. Furthermore, delaying the initiation of systemic NEP1–40 administration for up to 1 week after cord lesions does not limit the degree of axon sprouting and functional recovery. This indicates that the regenerative capacity of transected corticospinal tract axons persists for weeks after injury. Systemic Nogo-66 receptor antagonists have therapeutic potential for subacute CNS axonal injuries such as spinal cord trauma.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          15 May 2003
          : 23
          : 10
          : 4219-4227
          Affiliations
          Department of Neurology and Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520
          Article
          PMC6741116 PMC6741116 6741116 0234219
          10.1523/JNEUROSCI.23-10-04219.2003
          6741116
          12764110
          Copyright © 2003 Society for Neuroscience 0270-6474/03/234219-09.00/0
          Categories
          Development/Plasticity/Repair
          Custom metadata
          4219
          ARTICLE

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