Heme oxygenase 2 deficiency increases brain swelling and inflammation after intracerebral hemorrhage

J. Wang, S. Doré

Research output: Contribution to journalArticlepeer-review

Abstract

Intracerebral hemorrhage (ICH) remains a major medical problem and currently has no effective treatment. Hemorrhaged blood is highly toxic to the brain, and catabolism of the pro-oxidant heme, mainly released from hemoglobin, is critical for the resolution of hematoma after ICH. The degradation of the pro-oxidant heme is controlled by heme oxygenase (HO). We have previously reported a neuroprotective role for HO2 in early brain injury after ICH; however, in vivo data that specifically address the role of HO2 in brain edema and neuroinflammation after ICH are absent. Here, we tested the hypothesis that HO2 deletion would exacerbate ICH-induced brain edema, neuroinflammation, and oxidative damage. We subjected wild-type (WT) and HO2 knockout (-/-) mice to the collagenase-induced ICH model. Interestingly, HO2-/- mice had enhanced brain swelling and neuronal death, although HO2 deletion did not increase collagenase-induced bleeding; the exacerbation of brain injury in HO2-/- mice was also associated with increases in neutrophil infiltration, microglial/macrophage and astrocyte activation, DNA damage, peroxynitrite production, and cytochrome c immunoreactivity. In addition, we found that hemispheric enlargement was more sensitive than brain water content in the detection of subtle changes in brain edema formation in this model. Combined, these novel findings extend our previous observations and demonstrate that HO2 deficiency increases brain swelling, neuroinflammation, and oxidative damage. The results provide additional evidence that HO2 plays a critical protective role against ICH-induced early brain injury.

Original languageEnglish (US)
Pages (from-to)1133-1141
Number of pages9
JournalNeuroscience
Volume155
Issue number4
DOIs
StatePublished - Sep 9 2008

Keywords

  • astrocytes
  • blood
  • brain edema
  • hemispheric enlargement
  • reactive oxygen species
  • stroke

ASJC Scopus subject areas

  • Neuroscience(all)

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