orrhage, consequently disrupting the blood-spinal cord barrier, which normally helps protect the CNS. Rapid bleeding into the normal fluid-filled spaces of the spinal cord contributes to local edema. As the swelling within the confined space of the vertebral canal continues, it impinges on and further compromises nerve cells. Other important vascular changes are vasospasm, which is a narrowing of the blood vessels that often decreases blood flow by 80 percent (Anthes et al., 1996) and small-vessel thrombosis (Koyanagi et al., 1993). These vascular perturbations result in ischemia (i.e., deprivation of neurons and other cells of the oxygen and the other nutrients that they need to survive). Perhaps because it is more vascularized, the spinal cord’s gray matter (which contains neuron cell bodies) is far more necrotic after injury than the white matter, which contains large tracts of myelinated fibers (axons) that traverse up and down the spinal cord (Wolman, 1965).
The secondary phase sets in minutes after injury and lasts for weeks. During this phase the area of injury markedly expands. The secondary phase features a continuation of some events from the acute phase—electrolyte shifts, edema, and necrotic cell death—as well as novel ones, including the formation of free radicals, delayed calcium influx, immune system response (inflammation), and apoptotic cell death.
Free-radical formation, usually from oxygen atoms, gives rise to a series of pathological reactions inside cells, including the breakdown of lipids in the cell membrane, a process known as lipid peroxidation. The cell tolerates some degree of lipid peroxidation, but if it is substantial, the cell membrane becomes so disrupted that it bursts and dies. As it dies, the cell spills its contents into the extracellular space, which then threaten neighboring cells. For example, the spillage of the neurotransmitter glutamate can cause the death of nearby cells. If free radical attack does not lyse (burst) the cell membrane, it can invoke other types of damage. Free radicals, for example, can also attack membrane enzymes, distort ion gradients across the cell membrane, and damage genes.
The process of free-radical formation from oxygen begins in the mitochondria, a specialized portion of the cell devoted to converting oxygen into energy-rich molecules. Injury brings an influx of calcium into the cell, which can trigger the process of free-radical formation (Young, 1992). Oxygen atoms lose one of their outermost electrons and become highly reactive. To become more stable, they lure electrons from nearby atoms. In