Distinct role of heme oxygenase-1 in early-and late-stage intracerebral hemorrhage in 12-month-old mice

Zhen Zhang, Yuejia Song, Ze Zhang, Danyang Li, Hong Zhu, Rui Liang, Yunhe Gu, Yuxin Pang, Jiping Qi, He Wu, Jian Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. Heme oxygenase-1 (HO-1), the key enzyme in heme degradation, is highly expressed after ICH, but its role is still unclear. In this study, we used an HO-1 inducer and inhibitor to test the role of HO-1 in different stages of ICH in vivo and in vitro. In the early stage of ICH, high HO-1 expression worsened the outcomes of mice subjected to the collagenase-induced ICH model. HO-1 increased brain edema, white matter damage, neuronal death, and neurobehavioral deficits. Furthermore, elevated HO-1 increased inflammation, oxidative stress, matrix metalloproteinase-9/2 activity, and iron deposition. In the later stage of ICH, long-term induction of HO-1 increased hematoma absorption, angiogenesis, and recovery of neurologic function. We conclude that HO-1 activation mediates early brain damage after ICH but promotes neurologic function recovery in the later stage of ICH.

Original languageEnglish (US)
Pages (from-to)25-38
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • Inflammation
  • angiogenesis
  • intracerebral hemorrhage
  • matrix proteins
  • microglia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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