Heme oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury

Edward F. Chang, Ronald J. Wong, Hendrik J. Vreman, Takuji Igarashi, Ethel Galo, Frank R Sharp, David K. Stevenson, Linda J. Noble-Haeusslein

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

After traumatic brain injury (TBI), substantial extracellular heme is released from hemoproteins during hemorrhage and cell injury. Heme oxygenase (HO) isozymes are thought to detoxify the pro-oxidant heme to the potent antioxidant, bilirubin. HO-1, the inducible isozyme, is expressed in glial populations after injury and may play a protective role. However, the role of HO-2, the predominant and constitutively expressed isozyme in the brain, remains unclear after TBI. We used a controlled cortical impact injury model to determine the extent and mechanism of damage between HO-2 knock-out (KO) (-/-) and wild-type (WT) (+/+) mice. The specific cellular and temporal expressions of HO-2 and HO-1 were characterized by immunocytochemistry and Western blots. HO-2 was immunolocalized in neurons both before and after TBI, whereas HO-1 was highly upregulated in glia only after TBI. HO activity determined by gas chromotography using brain sonicates from injured HO-2 KO mice was significantly less than that of HO-2 wild types, despite the induction of HO-1 expression after TBI. Cell loss was significantly greater in KO mice in areas including the cortex, the CA3 region of hippocampus, and the lateral dorsal thalamus. Furthermore, motor recovery after injury, as measured by the rotarod assay and an inclined beam-walking task, was compromised in the KO mice. Finally, brain tissue from injured HO-2 KO mice exhibited decreased ability to reduce oxidative stress, as measured with an Fe2+/ascorbic acid-mediated carbon monoxide generation assay for lipid peroxidation susceptibility. These findings demonstrate that HO-2 expression protects neurons against TBI by reducing lipid peroxidation via the catabolism of free heme.

Original languageEnglish (US)
Pages (from-to)3689-3696
Number of pages8
JournalJournal of Neuroscience
Volume23
Issue number9
StatePublished - May 1 2003
Externally publishedYes

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Keywords

  • Controlled cortical impact
  • Heme oxygenase-2
  • Heme-oxygenase-1
  • Lipid peroxidation
  • Oxidative stress
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chang, E. F., Wong, R. J., Vreman, H. J., Igarashi, T., Galo, E., Sharp, F. R., Stevenson, D. K., & Noble-Haeusslein, L. J. (2003). Heme oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury. Journal of Neuroscience, 23(9), 3689-3696.