Apoptosis and Secondary Damage After Experimental Spinal Cord Injury

Abstract

Spinal cord injury does not happen all at once. After the initial impact to the cord, secondary injury processes proceed to destroy additional tissue and kill cells at the margins of the expanding lesion. This progression of damage has been thought to be due principally to the spread of necrotic, passive cell death by membrane destruction and release of chemicals that attack cells. Recent evidence suggests that apoptosis, a form of genetically programmed cell death that occurs naturally during development and in the immune system, is involved in the pathophysiology of spinal cord injury (SCI) and other trauma to the CNS. Apoptosis occurs for many days and even weeks after injury, especially in the myelin-forming oligodendrocytes of the cord white matter. This may lead to demyelination and further dysfunction. Apoptosis of both neurons and oligodendrocytes represents a new target for pharmacological therapies that may be effective in the subacute as well as the acute stages of injury. In addition to programmed cell death, we note that there is cell proliferation and repair after SCI that includes new cells and some axonal regeneration. The presence of neural stem cells and a limited repair response in the adult cord represent another target for therapies.