Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage
Jian Wang,Sylvain Doré +1 more
TLDR
It is found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells, revealing a previously unrecognized role of HO- 1 in early brain injury after ICH.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.read more
Citations
More filters
Journal ArticleDOI
Ferroptosis as a target for protection against cardiomyopathy.
Xuexian Fang,Hao Wang,Hao Wang,Dan Han,Enjun Xie,Xiang Yang,Jiayu Wei,Shanshan Gu,Feng Gao,Nali Zhu,Xiangju Yin,Qi Cheng,Pan Zhang,Wei Dai,Jinghai Chen,Fuquan Yang,Huang-Tian Yang,Andreas Linkermann,Wei Gu,Junxia Min,Fudi Wang,Fudi Wang +21 more
TL;DR: It is discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy and Mitochondria-targeted antioxidant MitoTEMPO significantly rescued DOX cardiopathy, supporting oxidative damage of mitochondria as a major mechanism in ferroPTosis-induced heart damage.
Journal ArticleDOI
Intracerebral haemorrhage: mechanisms of injury and therapeutic targets
Richard F. Keep,Ya Hua,Guohua Xi +2 more
TL;DR: Important advances have been made in animal models of this disorder and in the understanding of mechanisms underlying brain injury after haemorrhage, and several therapeutic targets have subsequently been identified that are now being pursued in clinical trials.
Journal ArticleDOI
Molecular Pathophysiology of Cerebral Hemorrhage Secondary Brain Injury
Jaroslaw Aronowski,Xiurong Zhao +1 more
TL;DR: In this paper, the authors discuss the relevance of hematoma resolution processes as a target for ICH therapy and present potential clinically relevant molecular targets that could be harnessed to treat secondary injury associated with ICH injury.
Journal ArticleDOI
Modulators of microglial activation and polarization after intracerebral haemorrhage.
TL;DR: Key studies on modulators of microglial activation and polarization after ICH are summarized, including M1-like and M2-like microglia phenotype markers, transcription factors and key signalling pathways, and the evidence that therapeutic approaches aimed at modulating microglian function might mitigate ICH injury and improve brain repair is presented.
Journal ArticleDOI
Preclinical and clinical research on inflammation after intracerebral hemorrhage.
TL;DR: This review summarizes recent progress made in preclinical models of ICH, surveys preclinical and clinical studies of inflammatory cells (leukocytes, macrophages, microglia, and astrocytes) and inflammatory mediators and highlights the emerging areas of therapeutic promise.
References
More filters
Journal ArticleDOI
Heme oxygenase 1 is required for mammalian iron reutilization
Kenneth D. Poss,Susumu Tonegawa +1 more
TL;DR: Results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.
Journal ArticleDOI
Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury
Sylvain Doré,Masaaki Takahashi,Christopher D. Ferris,Lynda D. Hester,Daniel Guastella,Solomon H. Snyder +5 more
TL;DR: A neuroprotective role for BR formed from HO2, which is constitutive and highly concentrated in neurons, is demonstrated, and BR, an antioxidant, is neuroprot protective at nanomolar concentrations.
Journal ArticleDOI
Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage.
TL;DR: It is demonstrated that reduced ferrohemoglobin, while relatively innocuous to cultured endothelial cells, when oxidized to ferrihemoglobin (methemoglobin), greatly amplifies oxidant (H2O2)-mediated endothelial-cell injury.
Journal ArticleDOI
Inflammation after Intracerebral Hemorrhage
Jian Wang,Sylvain Doré +1 more
TL;DR: In this review, a summary of the available literature on the inflammatory responses after ICH is presented along with discussion of some of the emerging opportunities for potential therapeutic strategies.
Journal ArticleDOI
Collagenase-induced intracerebral hemorrhage in rats.
TL;DR: Collagenase-induced intracerebral hemorrhage is a reproducible animal model for the study of the effects of the hematoma and brain edema in rats and characterized the lesion by histology, brain water content, and behavior.