Antiapoptotic therapies in the treatment of spinal cord injury

Mechanical trauma to the spinal cord triggers events resulting in the death of neurons and glia over several weeks following the initial injury. It has been suggested that the prevention of delayed apoptosis after spinal cord injury (SCI) is likely to have a beneficial effect by reducing the extent of neuronal and oligodendroglial death, which would translate into better functional outcomes. Drugs acting at different levels in the apoptotic cascade (i.e., caspase inhibitors and antiapoptotic Bcl-x_L) have been shown to decrease apoptotic cell death, but benefits in functional outcomes result only when inflammation is also decreased. Furthermore, long-term antiapoptotic therapy can result in nonapoptotic death with necrotic features, which will further increase inflammation and worsen outcome. Even though neuroprotective therapies are one of the targets for the promotion of functional recovery after SCI, targeting only post-SCI apoptosis is unlikely to be as successful as more integrated interventions that also target inflammation.