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.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Bldg. 364-365, Baltimore, MD 21205, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Hean
authors.initials: H
authors.lastname: Zhuang
authors.forename: Sylvain
authors.initials: S
authors.lastname: Doré
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000633:toxicity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2