Apoptotic and anti-apoptotic mechanisms following spinal cord injury

Robert W. Keane, Susan Kraydieh, George Lotocki, John R Bethea, Stanislaw Krajewski, John C. Reed, W. Dalton Dietrich

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

A number of studies have provided evidence that cell death from moderate traumatic spinal cord injury (SCI) is regulated, in part, by apoptosis that involves the caspase family of cysteine proteases. However, little or no information is available about anti-apoptotic mechanisms mediated by the inhibitors of apoptosis (IAP) family of proteins that inhibit cell death pathways. In the present study, we examined caspase and IAP expression in spinal cords of rats subjected to moderate traumatic injury. Within 6 h after injury, caspase-8 and-9 (2 initiators of apoptosis) were predominantly present in gray matter neurons within the lesion epicenter. By 3 days following spinal cord injury (SCI), caspase-8 and-9 immunoreactivity was localized to gray and white matter cells, and by 7 days following SCI, both upstream caspases were expressed in cells within white matter or within foamy macrophages in gray matter. Caspase-3, an effector caspase, was evident in a few fragmented cells in gray matter at 24 h following injury and then localized to white matter in later stages. Thus, distinct patterns of caspase expression can be found in the spinal cord following injury. XIAP, clAP-1, and clAP-2, members of the IAP family, were constitutively expressed in the cord. Immunoblots of spinal cord extracts revealed that the processed forms of caspases-8 and-9 and cleavage of PARP are present as early as 6 h following trauma. The expression of caspases corresponded with the detection of cleavage of XIAP into 2 fragments following injury, clAP-1 and clAP-2 expression remained constant during early periods following SCI but demonstrated alterations by 7 days following SCI. Our data are consistent with the idea that XIAP may have a protective role within the spinal cord, and that alteration in cleavage of XIAP may regulate cell death following SCI.

Original languageEnglish (US)
Pages (from-to)422-429
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume60
Issue number5
DOIs
StatePublished - May 2001

Keywords

  • Apoptosis
  • Apoptosis inhibitors
  • Caspases
  • Spinal cord injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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