FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury.
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.
Nottingham
Stephanie
S
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, Kentuck, 40536-0084, USA.
Knapp
Pamela
P
Springer
Joe
J
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
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D016559:Tacrolimus