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.
|Number of pages||10|
|State||Published - 2002|
Bibliographical noteFunding 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.).
- Spinal cord injury
ASJC Scopus subject areas
- Developmental Neuroscience