Sustained induction of heme oxygenase-1 in the traumatized spinal cord

Oxidative stress contributes to secondary injury after spinal cord trauma. Among the consequences of oxidative stress is the induction of heme oxygena se-1 (HO-1), an inducible isozyme that metabolizes heme to iron, biliverdin , and carbon monoxide. Here we examine the induction of HO-1 in the hemisec ted spinal cord, a model that results in reproducible degeneration in the i psilateral white matter. HO-1 was induced in microglia and macrophages from 24 h to at least 42 days after injury. Within the first week after injury, HO-1 was induced in both the gray and the white matter. Thereafter, HO-1 e xpression was limited to degenerating fiber tracts. HSP70, a heat shock pro tein induced mainly by the presence of denatured proteins, was consistently colocalized with HO-1 in the microglia and macrophages. This study to demo nstrates long-term induction of HO-1 and HSP70 in microglia and macrophages after traumatic injury and an association between induction of HO-1 and Wa llerian degeneration. White matter degeneration is characterized by phagocy tosis of cellular debris and remodeling of surviving tissue. This results i n the metabolism, synthesis, and turnover of heme and heme proteins. Thus, sustained induction of HO-1 and HSP70 in microglia and macrophages suggests that tissue degeneration is an ongoing process, lasting 6 weeks and perhap s even longer. (C) 2000 Academic Press.