Modulation of the secondary injury process after spinal cord injury in Bach1-deficient mice by heme oxygenase-1: Laboratory investigation

Kiyotaka Yamada, Nobuhiro Tanaka, Kazuyoshi Nakanishi, Naosuke Kamei, Masakazu Ishikawa, Toshiyuki Mizuno, Kazuhiro Igarashi, Mitsuo Ochi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Object. 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. Methods. 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. Results. 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. Conclusions. 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.

Original languageEnglish
Pages (from-to)611-620
Number of pages10
JournalJournal of Neurosurgery: Spine
Volume9
Issue number6
DOIs
Publication statusPublished - 2008 Dec 1

Keywords

  • Bach1
  • Heme oxygenase
  • Knockout mouse
  • Motor evoked potential
  • Spinal cord injury

ASJC Scopus subject areas

  • Surgery
  • Neurology
  • Clinical Neurology

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