|
Z-DEVD-FMK is a tetrapeptide caspase inhibitor that is considered relatively selective for caspase-31, 2 and has been widely used in in vitro and in vivo models of acute injury to delineate roles for caspase 3 in neuronal cell death. Intracerebroventricular injections of Z-DEVD-FMK improved function after LFP3. Intraparenchymal infusion of Z-DEVD-FMK over several days after combined CCI and hypoxia reduced lesion size, although functional outcome was not significantly improved in this model4 (Clark et al., 2000).
Z-DEVD-FMK was a potent inhibitor of calpain and that improvement observed after treatment with Z-DEVD-FMK may reflect, at least in part, this action.
Early treatment with Z-DEVD-FMK improved neurologic function and reduced lesion volume. Z-DEVD-FMK reduces cell death and inhibits calpain in a model of in vitro necrosis and a cell free assay and Z-DEVD-FMK treatment inhibits calpain activity after TBI in vivo.
Z-DEVD-FMK improved neurologic function and reduced tissue damage at an injury severity that showed predominantly necrotic neuronal cell death with minimal evidence of caspase 3 activation. Moreover, effective treatment with Z-DEVD-FMK was associated with reduced calpain-mediated -spectrin degradation. Z-DEVD-FMK was also neuroprotective, at concentrations lower than those routinely used to inhibit caspase 3, in an in vitro model of necrotic neuronal cell death induced by maitotoxin.
|