Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury

Joe E. Springer, Robert D. Azbill, Pamela E. Knapp

Research output: Contribution to journalArticlepeer-review

408 Scopus citations

Abstract

Traumatic spinal cord injury often results in complete loss of voluntary motor and sensory function below the site of injury. The long-term neurological deficits after spinal cord trauma may be due in part to widespread apoptosis of neurons and oligodendroglia in regions distant from and relatively unaffected by the initial injury. The caspase family of cysteine proteases regulates the execution of the mammalian apoptotic cell death program. Caspase-3 cleaves several essential downstream substrates involved in the expression of the apoptotic phenotype in vitro, including gelsolin, PAK2, fodrin, nuclear lainins and the inhibitory subunit of DNA fragmentation factor. Caspase-3 activation in vitro can be triggered by upstream events, leading to the release of cytochrome c from the mitochondria and the subsequent transactivation of procaspase-9 by Apaf-1 (refs. 13-15). We report here that these upstream and downstream components of the caspase-3 apoptotic pathway are activated after traumatic spinal cord injury in rats, and occur early in neurons to the injury site and hours to days later in oligodendroglia adjacent to and distant from the injury site. Given these findings, targeting the upstream events of the caspase-3 cascade has therapeutic potential in the treatment of acute traumatic injury to the spinal cord.

Original languageEnglish
Pages (from-to)943-946
Number of pages4
JournalNature Medicine
Volume5
Issue number8
DOIs
StatePublished - Aug 1999

Bibliographical note

Funding Information:
Acknowledgments We thank X. Wang for suggestions, B. Maley for assistance with the confocal images, and D.M. Gash and J.P. Herman for critically reviewing earlier versions of the manuscript. These studies were supported by PHS grant NS-30248 (J.E.S.) and grants from the Kentucky Spinal Cord and Head Injury Research Trust (J.E..S and P.E.K.).

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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