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

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TitleGlial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey macaca fascicularis
AuthorsShi, F3
Zhu, H6
Yang, S1
Liu, Y6
Feng, Y6
Shi, J6
Xu, D1
Wu, W2
You, S4
Ma, Z3
Zou, J3
Lu, P3
Xu, XM3 5 6
Issue Date2009
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/neu
CitationJournal Of Neurotrauma, 2009, v. 26 n. 11, p. 2083-2096 [How to Cite?]
DOI: http://dx.doi.org/10.1089/neu.2008.0706
AbstractSpinal 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. © 2009, Mary Ann Liebert, Inc.
ISSN0897-7151
2011 Impact Factor: 3.654
2011 SCImago Journal Rankings: 0.275
DOIhttp://dx.doi.org/10.1089/neu.2008.0706
ISI Accession Number IDWOS:000272049600022
Funding AgencyGrant Number
Major State Basic Research Development Program of China2003CB515302
People's Liberation Army Clinical Center for Spinal Cord Injury
Kunming General Hospital of People's Liberation Army
Indiana Spinal Cord and Brain Injury Research Board (ISCBIRB)
Mari Hulman George Endowments
Funding Information:

This study was supported by the Major State Basic Research Development Program of China (973 Project; 2003CB515302), the People's Liberation Army Clinical Center for Spinal Cord Injury, Kunming General Hospital of People's Liberation Army, the Indiana Spinal Cord and Brain Injury Research Board (ISCBIRB), and the Mari Hulman George Endowments. We thank Dr. Stephen Onifer for critical reading of the manuscript, and Hongqi Zhang for excellent EM technical assistance.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorShi, F
dc.contributor.authorZhu, H
dc.contributor.authorYang, S
dc.contributor.authorLiu, Y
dc.contributor.authorFeng, Y
dc.contributor.authorShi, J
dc.contributor.authorXu, D
dc.contributor.authorWu, W
dc.contributor.authorYou, S
dc.contributor.authorMa, Z
dc.contributor.authorZou, J
dc.contributor.authorLu, P
dc.contributor.authorXu, XM
dc.date.accessioned2012-06-26T05:57:44Z
dc.date.available2012-06-26T05:57:44Z
dc.date.issued2009
dc.description.abstractSpinal 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. © 2009, Mary Ann Liebert, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Neurotrauma, 2009, v. 26 n. 11, p. 2083-2096 [How to Cite?]
DOI: http://dx.doi.org/10.1089/neu.2008.0706
dc.identifier.doihttp://dx.doi.org/10.1089/neu.2008.0706
dc.identifier.epage2096
dc.identifier.isiWOS:000272049600022
Funding AgencyGrant Number
Major State Basic Research Development Program of China2003CB515302
People's Liberation Army Clinical Center for Spinal Cord Injury
Kunming General Hospital of People's Liberation Army
Indiana Spinal Cord and Brain Injury Research Board (ISCBIRB)
Mari Hulman George Endowments
Funding Information:

This study was supported by the Major State Basic Research Development Program of China (973 Project; 2003CB515302), the People's Liberation Army Clinical Center for Spinal Cord Injury, Kunming General Hospital of People's Liberation Army, the Indiana Spinal Cord and Brain Injury Research Board (ISCBIRB), and the Mari Hulman George Endowments. We thank Dr. Stephen Onifer for critical reading of the manuscript, and Hongqi Zhang for excellent EM technical assistance.

dc.identifier.issn0897-7151
2011 Impact Factor: 3.654
2011 SCImago Journal Rankings: 0.275
dc.identifier.issue11
dc.identifier.pmid19456214
dc.identifier.scopuseid_2-s2.0-75449113278
dc.identifier.spage2083
dc.identifier.urihttp://hdl.handle.net/10722/149729
dc.identifier.volume26
dc.languageeng
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/neu
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Neurotrauma
dc.relation.referencesReferences in Scopus
dc.subject.meshAnimals
dc.subject.meshAxotomy
dc.subject.meshDisease Models, Animal
dc.subject.meshImmunohistochemistry
dc.subject.meshMacaca Fascicularis
dc.subject.meshMale
dc.subject.meshMicroscopy, Electron, Transmission
dc.subject.meshMyelin Sheath - Metabolism - Ultrastructure
dc.subject.meshNeuroglia - Metabolism
dc.subject.meshSpinal Cord Injuries - Metabolism - Pathology
dc.subject.meshWallerian Degeneration - Metabolism - Pathology
dc.titleGlial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey macaca fascicularis
dc.typeArticle
Author Affiliations
  1. Yunnan Laboratory Primates Inc.
  2. The University of Hong Kong
  3. Shanghai Jiaotong University
  4. The Fourth Military Medical University
  5. Indiana University
  6. General Hospital of People's Liberation Army