Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury

Traumatic spinal cord injury often results in complete loss of voluntary mo tor and sensory function below the site of injury. The long-term neurologic al deficits after spinal cord trauma may be due in part to widespread apopt osis of neurons and oligodendroglia in regions distant from and relatively unaffected by the initial injury(1-4). The caspase family of cysteine prote ases regulates the execution of the mammalian apoptotic cell death program( 5-7). Caspase-3 cleaves several essential downstream substrates involved in the expression of the apoptotic phenotype in vitro, including gelsolin, PA K2, fodrin, nuclear lamins and the inhibitory subunit of DNA fragmentation facto(8-12). Caspase-3 activation in vitro can be triggered by upstream eve nts, leading to the release of cytochrome c from the mitochondria and the s ubsequent transactivation of procaspase-9 by Apaf-1 (refs. 13-15). We repor t here that these upstream and downstream components of the caspase-3 apopt otic pathway are activated after traumatic spinal cord injury in rats, and occur early in (sic) the injury site and hours to days later in oligodendro glia adjacent to and distant from the injury site. Given these findings, ta rgeting the upstream events of the caspase-3 cascade has therapeutic potent ial in the treatment of acute traumatic injury to the spinal cord.