期刊
NEUROREHABILITATION AND NEURAL REPAIR
卷 22, 期 3, 页码 262-278出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1545968307308550
关键词
spinal cord injury; rubrospinal tract; NEP1-40
资金
- NICHD NIH HHS [T32HD07467, T32 HD007467] Funding Source: Medline
- NINDS NIH HHS [R01 NS039962-10, R01 NS039962, P50 NS024707, R01 NS042304-08, R01 NS056485, R01 NS056485-04, R01 NS042304, R37 NS033020-17, R37 NS033020, NS24707] Funding Source: Medline
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.
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