Distinct role of heme oxygenase-1 in early- and late-stage intracerebral hemorrhage in 12-month-old mice.
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.
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Zhen
Z
Zhang
Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Yuejia
Y
Song
Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Ze
Z
Zhang
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Danyang
D
Li
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Hong
H
Zhu
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Rui
R
Liang
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Yunhe
Y
Gu
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Yuxin
Y
Pang
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China wuher_2008@hotmail.com qijiping2003@163.com.
Jiping
J
Qi
Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, PR China wuher_2008@hotmail.com qijiping2003@163.com.
He
H
Wu
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Jian
J
Wang
D000375:Aging; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D017364:Collagenases / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000097:blood* / Q000378:metabolism; D051379:Mice; D020127:Recovery of Function / Q000187:drug effects; D013997:Time Factors
D051547:Heme Oxygenase-1; D017364:Collagenases
Inflammation; angiogenesis; intracerebral hemorrhage; matrix proteins; microglia