Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage

Jian Wang; Hean Zhuang; Sylvain Doré

doi:10.1016/j.nbd.2005.12.009

Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage

Jian Wang, Hean Zhuang, Sylvain Doré

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

Recent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in acute brain injury and ischemia. HO2, the main enzyme to degrade the pro-oxidant heme, was tested for its neuroprotective ability in postnatal neuronal cell cultures and in a model of collagenase-induced intracerebral hemorrhage. Genetic deletion of HO2 rendered cultured neurons 32% (P < 0.01) more vulnerable to hemin-induced toxicity, increased brain injury volume in mice by 30% (P < 0.05) at day 1 and by 67% (P < 0.05) at day 3, and worsened neurologic functions by 26% (P < 0.05) at day 1 and by 38% (P < 0.05) at day 3 following exposure to free heme liberated from hemorrhage. Together, these findings suggest that HO2 is a crucial neuroprotective enzyme in detoxifying high levels of heme from the brain and that further work is warranted to investigate potential therapeutic strategies that target HO2 in intracerebral hemorrhage.

Original language	English (US)
Pages (from-to)	473-476
Number of pages	4
Journal	Neurobiology of Disease
Volume	22
Issue number	3
DOIs	https://doi.org/10.1016/j.nbd.2005.12.009
State	Published - Jun 2006
Externally published	Yes

Keywords

Blood
Hemin
Intracerebral hemorrhage
Ischemia
Mouse
Stroke

ASJC Scopus subject areas

Neurology

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10.1016/j.nbd.2005.12.009

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title = "Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage",

abstract = "Recent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in acute brain injury and ischemia. HO2, the main enzyme to degrade the pro-oxidant heme, was tested for its neuroprotective ability in postnatal neuronal cell cultures and in a model of collagenase-induced intracerebral hemorrhage. Genetic deletion of HO2 rendered cultured neurons 32% (P < 0.01) more vulnerable to hemin-induced toxicity, increased brain injury volume in mice by 30% (P < 0.05) at day 1 and by 67% (P < 0.05) at day 3, and worsened neurologic functions by 26% (P < 0.05) at day 1 and by 38% (P < 0.05) at day 3 following exposure to free heme liberated from hemorrhage. Together, these findings suggest that HO2 is a crucial neuroprotective enzyme in detoxifying high levels of heme from the brain and that further work is warranted to investigate potential therapeutic strategies that target HO2 in intracerebral hemorrhage.",

keywords = "Blood, Hemin, Intracerebral hemorrhage, Ischemia, Mouse, Stroke",

author = "Jian Wang and Hean Zhuang and Sylvain Dor{\'e}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health (AT001836, AA014911, AT002113, and NS046400), the American Heart Association, the ABMR Foundation, and the Wine Institute. We are grateful to David Greenberg and It{\'e} Alonzo for technical help. We thank Dr. Raymond C. Koehler and all members of the Dor{\'e} laboratory for helpful discussions and critical reading of the manuscript. We also thank Tzipora Sofare and Claire Levine for their assistance in the manuscript.",

year = "2006",

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doi = "10.1016/j.nbd.2005.12.009",

language = "English (US)",

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pages = "473--476",

journal = "Neurobiology of Disease",

issn = "0969-9961",

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AU - Wang, Jian

AU - Zhuang, Hean

AU - Doré, Sylvain

N1 - Funding Information: This work was supported by grants from the National Institutes of Health (AT001836, AA014911, AT002113, and NS046400), the American Heart Association, the ABMR Foundation, and the Wine Institute. We are grateful to David Greenberg and Ité Alonzo for technical help. We thank Dr. Raymond C. Koehler and all members of the Doré laboratory for helpful discussions and critical reading of the manuscript. We also thank Tzipora Sofare and Claire Levine for their assistance in the manuscript.

PY - 2006/6

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N2 - Recent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in acute brain injury and ischemia. HO2, the main enzyme to degrade the pro-oxidant heme, was tested for its neuroprotective ability in postnatal neuronal cell cultures and in a model of collagenase-induced intracerebral hemorrhage. Genetic deletion of HO2 rendered cultured neurons 32% (P < 0.01) more vulnerable to hemin-induced toxicity, increased brain injury volume in mice by 30% (P < 0.05) at day 1 and by 67% (P < 0.05) at day 3, and worsened neurologic functions by 26% (P < 0.05) at day 1 and by 38% (P < 0.05) at day 3 following exposure to free heme liberated from hemorrhage. Together, these findings suggest that HO2 is a crucial neuroprotective enzyme in detoxifying high levels of heme from the brain and that further work is warranted to investigate potential therapeutic strategies that target HO2 in intracerebral hemorrhage.

AB - Recent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in acute brain injury and ischemia. HO2, the main enzyme to degrade the pro-oxidant heme, was tested for its neuroprotective ability in postnatal neuronal cell cultures and in a model of collagenase-induced intracerebral hemorrhage. Genetic deletion of HO2 rendered cultured neurons 32% (P < 0.01) more vulnerable to hemin-induced toxicity, increased brain injury volume in mice by 30% (P < 0.05) at day 1 and by 67% (P < 0.05) at day 3, and worsened neurologic functions by 26% (P < 0.05) at day 1 and by 38% (P < 0.05) at day 3 following exposure to free heme liberated from hemorrhage. Together, these findings suggest that HO2 is a crucial neuroprotective enzyme in detoxifying high levels of heme from the brain and that further work is warranted to investigate potential therapeutic strategies that target HO2 in intracerebral hemorrhage.

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KW - Intracerebral hemorrhage

KW - Ischemia

KW - Mouse

KW - Stroke

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Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage

Abstract

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