Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage
Departments of 1Anesthesiology/Critical Care Medicine and 2Neuroscience, Johns Hopkins University, Baltimore, MD, USA
Correspondence to: Jian Wang, MD, PhD, Instructor, Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, 720 Rutland Ave, Traylor Bldg 809, Baltimore, MD 21205, USA and Sylvain Doré, PhD, Associate Professor, Departments of Anesthesiology/Critical Care Medicine and Neuroscience, Johns Hopkins University, School of Medicine, 720 Rutland Ave, Ross 365, Baltimore, MD 21205, USA E-mail: jwang79{at}jhmi.edu; sdore{at}jhmi.edu
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.
Key Words: antioxidants; blood; hemin; HO-1; reactive oxygen species
Abbreviations: HO, heme oxygenase; ICH, intracerebral haemorrhage; MAP2, Microtubule-associated protein-2; MPO, myeloperoxidase; 8-OHG, 8-hydroxyguanosine; ROS, reactive oxygen species
Received October 16, 2006. Revised March 23, 2007. Accepted March 28, 2007.