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.
Guth
L
L
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville 22908, USA. lloydguth@erols.com
Zhang
Z
Z
Steward
O
O
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D051381:Rats; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*; D014855:Wallerian Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D000893:Anti-Inflammatory Agents