Rapid calpain I activation and cytoskeletal protein degradation following traumatic spinal cord injury: Attenuation with riluzole pretreatment

Joe E. Springer, Robert D. Azbill, Sarah E. Kennedy, Jones George, James W. Geddes

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

Immunocytochemical and immunoblotting techniques were used to investigate calpain I activation and the stability of the calpain-sensitive cytoskeletal proteins microtubule-associated protein 2 (MAP2) and spectrin at 1, 4, and 24 h after contusion injury to the spinal cord. Spinal cord injury resulted in the activation of cal-pain I at all time points examined, with the highest level of activation occurring at 1 h. At the same early time point, there was a loss of dendritic MAP2 staining in spinal cord sections, accompanied by pronounced perikaryal accumulation. The loss in MAP2 staining in the injured spinal cord progressed over the 24-h survival period to affect regions 3 mm distant to the site of injury. The presence of calpain I- specific spectrin degradation was apparent in neuronal cell bodies and fibers as early as 1 h after injury, with the most intense staining occurring within and juxtaposed to the injury site. Spectrin break-down products in neuronal cell bodies declined rapidly at 4 h and were nearly undetectable at 24 h after injury. Immunoblot studies confirmed the immunocytochemical results by demonstrating a significant increase in calpain I activation, a significant decrease in MAP2 levels, and a significant increase in spectrin breakdown. Finally, treatment of animals with riluzole, an inhibitor of glutamate release, before surgery reduced significantly the loss of MAP2 levels observed at 24 h after injury. These results demonstrate that Ca2+ - dependent protease activation and degradation of critical cytoskeletal proteins are early events after spinal cord injury and that treatments that minimize the actions of glutamate may limit their breakdown.

Original languageEnglish
Pages (from-to)1592-1600
Number of pages9
JournalJournal of Neurochemistry
Volume69
Issue number4
DOIs
StatePublished - Oct 1997

Keywords

  • CNS injury
  • Calcium
  • Calpain I
  • Cytoskeleton
  • Glutamate
  • Microtubule-associated protein 2
  • Riluzole
  • Spectrin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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