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.
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.