Distinct role of heme oxygenase-1 in early- and late-stage intracerebral hemorrhage in 12-month-old mice
Open accessAbstract
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.
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Long-term induction of Hmox1 promotes the resolution of ICH.
“Indeed, long-term induction of Hmox1 promotes the resolution of ICH [260].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [260]
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References 48 · Cited by 89
- Authors
- Zhang, Z., Song, Y., Zhang, Z., Li, D., Zhu, H., Liang, R., Gu, Y., Pang, Y., Qi, J., Wu, H., & Wang, J.
- Affiliations
- First Affiliated Hospital of Harbin Medical University (CN)
- Johns Hopkins University (US)
- Corresponding author
- Qi, Jiping
- Wu, He
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2016-07-20
- Volume
- 37
- Issue
- 1
- Pages
- 25-38
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC5363754
- OpenAlex
- W2430255266
- Cited by
- 89
- References
- 48
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 5 · 2023: 11 · 2022: 9 · 2021: 9 · 2020: 7 · 2019: 12 · 2018: 12 · 2017: 9 · 2016: 1
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-07-06)
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- heme oxygenase-1, intracerebral hemorrhage, collagenase-induced hemorrhage, cerebral edema, white matter injury, neuronal cell death, neuroinflammation, oxidative stress, MMP-9, MMP-2, iron accumulation, hematoma absorption, angiogenesis, neurological recovery
- MeSH terms
- Aging, Animals, Brain Injuries, Cerebral Hemorrhage, Time Factors, Collagenases, Recovery of Function, Mice, Heme Oxygenase-1
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