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成年猕猴颈脊髓单侧横断后红核脊髓神经元的命运:一种中和Nogo-A的抗体治疗的效果

Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: effects of an antibody treatment neutralizing Nogo-A.

作者信息

Wannier-Morino P, Schmidlin E, Freund P, Belhaj-Saif A, Bloch J, Mir A, Schwab M E, Rouiller E M, Wannier T

机构信息

Unit of Physiology and Program in Neurosciences, Department of Medicine, Faculty of Sciences, University of Fribourg, Chemin du Musée 5, Fribourg, Switzerland.

出版信息

Brain Res. 2008 Jun 27;1217:96-109. doi: 10.1016/j.brainres.2007.11.019. Epub 2007 Nov 22.

Abstract

The present study describes in primates the effects of a spinal cord injury on the number and size of the neurons in the magnocellular part of the red nucleus (RNm), the origin of the rubrospinal tract, and evaluates whether a neutralization of Nogo-A reduces the lesioned-induced degenerative processes observed in RNm. Two groups of monkeys were subjected to unilateral section of the spinal cord affecting the rubrospinal tract; one group was subsequently treated with an antibody neutralizing Nogo-A; the second group received a control antibody. Intact animals were also included in the study. Counting neurons stained with a monoclonal antibody recognizing non-phosphorylated epitopes on neurofilaments (SMI-32) indicated that their number in the contralesional RNm was consistently inferior to that in the ipsilesional RNm, in a proportion amounting up to 35%. The lesion also induced shrinkage of the soma of the neurons detected in the contralesional RNm. Infusing an anti-Nogo-A antibody at the site of the lesion did not increase the proportion of SMI-32 positive rubrospinal neurons in the contralesional RNm nor prevent shrinkage.

摘要

本研究描述了灵长类动物脊髓损伤对红核大细胞部(RNm)神经元数量和大小的影响,红核脊髓束起源于此,并评估了Nogo-A的中和是否能减少在RNm中观察到的损伤诱导的退行性过程。两组猴子接受了影响红核脊髓束的单侧脊髓横断;一组随后用中和Nogo-A的抗体进行治疗;第二组接受对照抗体。完整动物也纳入了研究。用识别神经丝上非磷酸化表位的单克隆抗体(SMI-32)染色的神经元计数表明,对侧RNm中神经元数量始终低于同侧RNm,比例高达35%。损伤还导致对侧RNm中检测到的神经元胞体萎缩。在损伤部位注入抗Nogo-A抗体既没有增加对侧RNm中SMI-32阳性红核脊髓神经元的比例,也没有防止萎缩。

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