Heme oxygenase-I exacerbates early brain injury after intracerebral haemorrhage

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-I to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, IHO- I proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endlothelial cells. Remarkably, the injury volume was significantly smaller in IH10- I knockout (HO-I-/-) 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-I-/- 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- I in early brain injury after ICH.Thus, modulation of HO-I signalling should be assessed further in clinical settings, especially for haemorrhagic states.