title: FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury.
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.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, Kentuck, 40536-0084, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nottingham
authors.forename: Pamela
authors.initials: P
authors.lastname: Knapp
authors.forename: Joe
authors.initials: J
authors.lastname: Springer
mesh_terms: D000818:Animals; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000201:enzymology*; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D016559:Tacrolimus