Glial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey macaca fascicularis

Fujun Shi, Hui Zhu, Senfu Yang, Yansheng Liu, Yaping Feng, Jihong Shi, Dingze Xu, Wutian Wu, Siwei You, Zhengwen Ma, Jian Zou, Peihua Lu, Xiao-Ming Xu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Spinal cord injury (SCI) in mammals not only damages the focal area, but also leads to wallerian degeneration (WD) of axons and myelin distal to the injury. In the present study, we investigated cellular responses within areas of WD of a sensory pathway, the fasciculus gracilis, after a T8-9 lateral spinal hemisection in the adult monkey Macaca fascicularis. Spinal cord segments rostral and caudal to the injury at two clinically-relevant time points, 1 week and 4 weeks post-SCI, representing subacute and chronic stages, respectively, were examined. We observed marked axon degeneration in the areas of WD at the subacute stage, and minimal axonal neurofilament staining at the chronic stage. At the ultrastructural level, however, many degenerating axonal profiles remained at the chronic stage. Myelin breakdown was a much-delayed process. A large number of residual myelin sheaths was observed at the chronic stage. In contrast to rodents, a substantial astrogliotic response was not found in the WD regions up to 4 weeks post-injury. Microglia activation was evident in the WD areas at the subacute stage, and was enhanced at the chronic stage. However, the lack of round reactive microglia/macrophages in these regions suggests that microglial activation was either delayed or incomplete. Thus it appears that many pathological characteristics of WD in monkeys are much delayed compared to those in rodents, but are similar to those in humans. Our results suggest that non-human primate SCI models are useful for evaluating repair strategies before they are translated to clinical trials of human SCI.

Original languageEnglish
Pages (from-to)2083-2096
Number of pages14
JournalJournal of Neurotrauma
Volume26
Issue number11
DOIs
StatePublished - Nov 1 2009

Fingerprint

Wallerian Degeneration
Macaca fascicularis
Myelin Sheath
Neuroglia
Haplorhini
Spinal Cord
Spinal Cord Injuries
Microglia
Axons
Rodentia
Wounds and Injuries
Intermediate Filaments
Primates
Mammals
Macrophages
Clinical Trials
Staining and Labeling

Keywords

  • Astrocytes
  • Axons
  • Macaca fascicularis
  • Macrophages
  • Microglia
  • Monkey
  • Myelin
  • Spinal cord injury
  • Wallerian degeneration

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Glial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey macaca fascicularis. / Shi, Fujun; Zhu, Hui; Yang, Senfu; Liu, Yansheng; Feng, Yaping; Shi, Jihong; Xu, Dingze; Wu, Wutian; You, Siwei; Ma, Zhengwen; Zou, Jian; Lu, Peihua; Xu, Xiao-Ming.

In: Journal of Neurotrauma, Vol. 26, No. 11, 01.11.2009, p. 2083-2096.

Research output: Contribution to journalArticle

Shi, F, Zhu, H, Yang, S, Liu, Y, Feng, Y, Shi, J, Xu, D, Wu, W, You, S, Ma, Z, Zou, J, Lu, P & Xu, X-M 2009, 'Glial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey macaca fascicularis', Journal of Neurotrauma, vol. 26, no. 11, pp. 2083-2096. https://doi.org/10.1089/neu.2008.0706
Shi, Fujun ; Zhu, Hui ; Yang, Senfu ; Liu, Yansheng ; Feng, Yaping ; Shi, Jihong ; Xu, Dingze ; Wu, Wutian ; You, Siwei ; Ma, Zhengwen ; Zou, Jian ; Lu, Peihua ; Xu, Xiao-Ming. / Glial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey macaca fascicularis. In: Journal of Neurotrauma. 2009 ; Vol. 26, No. 11. pp. 2083-2096.
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AU - Xu, Dingze

AU - Wu, Wutian

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AB - Spinal cord injury (SCI) in mammals not only damages the focal area, but also leads to wallerian degeneration (WD) of axons and myelin distal to the injury. In the present study, we investigated cellular responses within areas of WD of a sensory pathway, the fasciculus gracilis, after a T8-9 lateral spinal hemisection in the adult monkey Macaca fascicularis. Spinal cord segments rostral and caudal to the injury at two clinically-relevant time points, 1 week and 4 weeks post-SCI, representing subacute and chronic stages, respectively, were examined. We observed marked axon degeneration in the areas of WD at the subacute stage, and minimal axonal neurofilament staining at the chronic stage. At the ultrastructural level, however, many degenerating axonal profiles remained at the chronic stage. Myelin breakdown was a much-delayed process. A large number of residual myelin sheaths was observed at the chronic stage. In contrast to rodents, a substantial astrogliotic response was not found in the WD regions up to 4 weeks post-injury. Microglia activation was evident in the WD areas at the subacute stage, and was enhanced at the chronic stage. However, the lack of round reactive microglia/macrophages in these regions suggests that microglial activation was either delayed or incomplete. Thus it appears that many pathological characteristics of WD in monkeys are much delayed compared to those in rodents, but are similar to those in humans. Our results suggest that non-human primate SCI models are useful for evaluating repair strategies before they are translated to clinical trials of human SCI.

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