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


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.