The unique histopathological responses of the injured spinal cord. Implications for neuroprotective therapy.

Tissue destruction at the primary site of a spinal cord injury leads to persistent necrosis that progressively enlarges the lesion. Steroids attenuate this necrotizing process and promote tissue repair even though such anti-inflammatory drugs interfere with wound healing in non-CNS organs. To address this paradox, the spinal cord of rats and mice was crushed extradurally and the effects of the following anti-inflammatory agents studied by light microscopical image analysis: allopurinol, aminoguanidine, indomethacin, a bacterial lipopolysaccharide, naproxen, and pregnenolone. The contribution of Wallerian degeneration to progressive necrosis was studied in a mutant mouse strain (WldS) that is characterized by delayed Wallerian degeneration. In rats, the anti-inflammatory agents selectively attenuated progressive necrosis and encouraged wound healing. In mice, considerable tissue repair occurred without pharmacological intervention; this wound-healing process was delayed in the mutant WldS strain. Since spinal cord injury results in concomitant tissue necrosis and wound healing, a goal of neuroprotective therapy is to regulate the dynamic balance between these destructive and reparative processes.