Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage.
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.
Wang
Jian
J
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Bldg. 364-365, Baltimore, MD 21205, USA.
Zhuang
Hean
H
Doré
Sylvain
S
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*
D018696:Neuroprotective Agents; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2