Oxidative stress contributes to secondary injury after spinal cord injury (SCI). The expression of heme oxygenase-1 (HO-1), which protects cells from various insults including oxidative stress, is upregulated in injured spinal cords. Mice deficient in Bach1 (Bach1−/−), a transcriptional repressor of the HO-1 and beta-globin genes, express high levels of HO-1 mRNA and protein in various organs. The authors hypothesized that HO-1 modulates the secondary injury process after SCI in Bach1−/− mice.
Male C57BL/6 (wild-type) and homozygous Bach1−/− C57BL/6 mice were subjected to moderate SCI, and differences in hindlimb motor function, and electrophysiological, molecular biological, and histopathological changes were assessed for 2 weeks.
Functional recovery was greater, and motor evoked potentials were significantly larger in Bach1−/− mice than in wild-type mice throughout the observation period. The expression of HO-1 mRNA in the spinal cord was significantly increased in both mice until 3 days after injury, and it was significantly higher in Bach1−/− mice than in wild-type mice at every assessment point. Histological examination using Luxol fast blue staining at 1 day after injury showed that the injured areas were smaller in Bach1−/− mice than in wild-type mice. The HO-1 immunoreactivity was not detected in uninjured spinal cord, but 3 days postinjury the number of HO-1–immunoreactive cells was obviously higher in the injured area in both mice, particularly in Bach1−/− mice. The HO-1 was primarily induced in microglia/macrophage in both mice.
These results suggest that HO-1 modulates the secondary injury process, and high HO-1 expression may preserve spinal cord function in the early stages after SCI in Bach1−/− mice. Treatment that induces HO-1 expression at these early stages may preserve the functional outcome after SCI.
Abbreviations used in this paper: Bach1−/− = Bach1-deficient; BBB = Basso-Beattie-Bresnahan; HO-1 = heme oxygenase-1; MEP = motor evoked potential; PCR = polymerase chain reaction; RT = reverse transcription; SCI = spinal cord injury.
Address correspondence to: Kiyotaka Yamada, M.D., Department of Orthopaedic Surgery, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, 734-8551, Japan. email:
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