Fk506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury

Stephanie Nottingham, Pamela Knapp, Joe Springer

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The focus of this study is to examine the ability of FK506, an immunosuppressant that inhibits calcineurin activation, to limit caspase-3 activation in oligodendroglia following spinal cord injury (SCI). To better establish a role for calcineurin and caspase-3 activation in oligodendroglia following SCI, rats received a contusion injury to the spinal cord followed by treatment with FK506 or rapamycin (another immunosuppressant with no detectable inhibitory action on calcineurin activation). Animals were then sacrificed at 8 days postinjury and spinal cord tissue was processed using immunofluorescence histochemistry to examine cellular caspase-3 activation in ventral and dorsal white matter. In all treatment groups, numerous oligodendroglia were found to express the activated form of caspase-3 in regions proximal and distal to the injury epicenter. However, our findings suggest that treatment with FK506, but not rapamycin reduces the number of oligodendroglia expressing activated caspase-3 and increases the number of surviving oligodendroglia in dorsal white matter. These results provide initial evidence that agents that reduce the actions of calcineurin and subsequent caspase-3 activation may prove beneficial in the treatment of traumatic SCI.

Original languageEnglish
Pages (from-to)242-251
Number of pages10
JournalExperimental Neurology
Volume177
Issue number1
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
The authors thank Jacqueline C. Bresnahan, Ph.D., for sharing the results of a recently submitted study (67) that support our observations of oligodendroglial cell loss following SCI. This work was supported by NIH Grant NS-40015 and grants from the Kentucky Spinal Cord and Head Injury Research Trust (J.E.S.) and the National Multiple Sclerosis Society (P.E.K.).

Keywords

  • Apoptosis
  • Calcineurin
  • Caspase-3
  • FK506
  • Glutamate
  • Oligodendroglia
  • Rapamycin
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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