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Neurorehabil Neural Repair. 2008 May-Jun;22(3):262-78. Epub 2007 Nov 30.

Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat.

Author information

1
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA. yc94@drexel.edu

Abstract

OBJECTIVE:

The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST).

METHODS:

Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry.

RESULTS:

Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group.

CONCLUSIONS:

NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons.

PMID:
18056009
PMCID:
PMC2853251
DOI:
10.1177/1545968307308550
[Indexed for MEDLINE]
Free PMC Article

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