Experimental analysis of progressive necrosis after spinal cord trauma in the rat: etiological role of the inflammatory response.
Progressive tissue necrosis is a unique reaction to spinal cord trauma in which the site of injury is gradually transformed into a large, cavity-filled lesion. The earliest histopathological changes after injury include a widely disseminated extravasation of erythrocytes and neutrophils. To test whether such an inflammatory reaction might initiate progressive necrosis, we examined the effects of the following anti-inflammatory treatments: allopurinol (Ap) to inhibit injury-induced xanthine oxidase, indomethacin (I) or naproxen to inhibit constitutive and inducible cyclooxygenase, aminoguanidine (Ag) to inhibit inducible nitric oxide synthase, pregnenolone (P) as a precursor steroid, and a bacterial lipopolysaccharide (L) to stimulate secretory activities of glial cells and macrophages. The spinal cord of adult rats was crushed at T8 with jeweler's forceps and, after 3 or 21 days of treatment, the cords were studied quantitatively by light microscopical image analysis. Ag, Ag+I, or Ap significantly reduced the size of the primary lesion at 3 days postoperatively, while P+L+I did so only after 21 days of treatment. A secondary lesion developed in the dorsal column and gradually extended for many millimeters rostral and caudal from the primary lesion. The size of the dorsal column lesion was diminished by 3-day treatment with Ap and by 21-day treatment with Ap or P+L+I, but Ag or Ag+I had no effect. We conclude that (a) progressive necrosis is initiated and maintained by inflammatory mechanisms and (b) for this reason, treatment with specific anti-inflammatory agents selectively attenuates various components of the necrotizing process.
Zhang
Z
Z
Department of Biology, The College of William and Mary, Williamsburg, Virginia 23187, USA.
Krebs
C J
CJ
Guth
L
L
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D009288:Naproxen / Q000494:pharmacology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D009288:Naproxen; D000493:Allopurinol