title: Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage.
abstract: Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1-/-) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1-/- mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, 720 Rutland Ave, Traylor Bldg 809, Baltimore, MD 21205, USA. jwang79@jhmi.edu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Sylvain
authors.initials: S
authors.lastname: Doré
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D006454:Hemoglobins / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D006454:Hemoglobins; D051547:Heme Oxygenase-1