TY - JOUR
T1 - Modulation of the secondary injury process after spinal cord injury in Bach1-deficient mice by heme oxygenase-1
T2 - Laboratory investigation
AU - Yamada, Kiyotaka
AU - Tanaka, Nobuhiro
AU - Nakanishi, Kazuyoshi
AU - Kamei, Naosuke
AU - Ishikawa, Masakazu
AU - Mizuno, Toshiyuki
AU - Igarashi, Kazuhiro
AU - Ochi, Mitsuo
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
KW - Bach1
KW - Heme oxygenase
KW - Knockout mouse
KW - Motor evoked potential
KW - Spinal cord injury
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U2 - 10.3171/SPI.2008.10.08488
DO - 10.3171/SPI.2008.10.08488
M3 - Article
C2 - 19035757
AN - SCOPUS:58849147989
VL - 9
SP - 611
EP - 620
JO - Journal of Neurosurgery: Spine
JF - Journal of Neurosurgery: Spine
SN - 1547-5654
IS - 6
ER -