Heme–Hemopexin Scavenging Is Active in the Brain and Associates With Outcome After Subarachnoid Hemorrhage

Garland, Patrick; Durnford, Andrew; Okemefuna, Azubuike I.; Dunbar, J. R.; Nicoll, James A. R.; Galea, James; Boche, Delphine; Bulters, Diederik; Galea, Ian

doi:10.1161/strokeaha.115.011956

Cited by 51 publications

(50 citation statements)

References 13 publications

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“…Haem is catabolized by haem oxygenases into biliverdin, carbon monoxide and iron. Activation of LRP1 scavenging system in humans has favourable effects after subarachnoid haemorrhage (SAH) . Recently, it is confirmed that the activation of the LRP1 system is beneficial in experimental ICH .…”

Section: Hx–haem–lrp1mentioning

confidence: 99%

Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic

Wang

Sun

et al. 2017

J Cellular Molecular Medi

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The products of erythrocyte lyses, haemoglobin (Hb) and haem, are recognized as neurotoxins and the main contributors to delayed cerebral oedema and tissue damage after intracerebral haemorrhage (ICH). Finding a means to efficiently promote absorption of the haemolytic products (Hb and haem) around the bleeding area in the brain through stimulating the function of the body's own garbage cleaning system is a novel clinical challenge and critical for functional recovery after ICH. In this review, available information of the brain injury mechanisms underlying ICH and endogenous haematoma scavenging system is provided. Meanwhile, potential intervention strategies are discussed. Intracerebral blood itself has ‘toxic’ effects beyond its volume effect after ICH. Haptoglobin–Hb–CD163 as well as haemopexin–haem–LRP1 is believed to be the most important endogenous scavenging pathway which participates in blood components resolution following ICH. PPARγ–Nrf2 activates the aforementioned clearance pathway and then accelerates haematoma clearance. Meanwhile, the scavenger receptors as novel targets for therapeutic interventions to treat ICH are also highlighted.

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Section: Hx–haem–lrp1mentioning

confidence: 99%

Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic

Wang

Sun

et al. 2017

J Cellular Molecular Medi

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“…The haem–haemopexin scavenging has been demonstrated to be active and potentially harmful following SAH. CD91, the receptor for haemopexin, is positively correlated with iron deposition in brain tissue, which in turn is negatively correlated with neurological outcome 68. This system may be responsible for intracellular accumulation of iron that results following SAH.…”

Section: Subarachnoid Haemorrhagementioning

confidence: 99%

Brain iron overload following intracranial haemorrhage

et al. 2016

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Intracranial haemorrhages, including intracerebral haemorrhage (ICH), intraventricular haemorrhage (IVH) and subarachnoid haemorrhage (SAH), are leading causes of morbidity and mortality worldwide. In addition, haemorrhage contributes to tissue damage in traumatic brain injury (TBI). To date, efforts to treat the long-term consequences of cerebral haemorrhage have been unsatisfactory. Incident rates and mortality have not showed significant improvement in recent years. In terms of secondary damage following haemorrhage, it is becoming increasingly apparent that blood components are of integral importance, with haemoglobin-derived iron playing a major role. However, the damage caused by iron is complex and varied, and therefore, increased investigation into the mechanisms by which iron causes brain injury is required. As ICH, IVH, SAH and TBI are related, this review will discuss the role of iron in each, so that similarities in injury pathologies can be more easily identified. It summarises important components of normal brain iron homeostasis and analyses the existing evidence on iron-related brain injury mechanisms. It further discusses treatment options of particular promise.

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“…After SAH, the brain is exposed to high concentrations of hemoglobin as erythrocytes lyse (26). Hemoglobin and heme are then captured by macrophages in the form of hemoglobin-haptoglobin and heme-hemopexin complexes via the hemoglobin scavenger receptor CD163 and hemopexin scavenger receptor CD91, respectively (27, 28). Heme-oxygenase-1 (HO-1) is a key inducible enzyme for heme degradation and iron release.…”

Section: Introductionmentioning

confidence: 99%

MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage

Guo

Wilkinson

Thompson

et al. 2016

Transl. Stroke Res.

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A number of mechanisms have been proposed for the early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated the radiographic characteristics and influence of gender on early brain injury after experimental SAH. SAH was induced by endovascular perforation in male and female rats. Magnetic resonance imaging was performed in a 7.0-T Varian MR scanner at 24 hours after SAH. The occurrence and size of T2 lesions, ventricular dilation and white matter injury (WMI) was determined on T2 weighted images (T2WI). The effects of SAH on heme oxygenase-1 and fibrin/fibrinogen were examined by Western blotting and immunohistochemistry. SAH severity was assessed using a MRI grading system and neurological function was evaluated according to a modified Garcia’s scoring system. T2-hyperintensity areas and enlarged ventricles were observed in T2WI coronal sections 24 hours after SAH. The overall incidence of T2-lesions, WMI and hydrocephalus was 54, 20 and 63%, respectively. Female rats had a higher incidence of T2-hyperintensity lesions and hydrocephalus, as well as larger T2 lesion volumes and higher average ventricular volume. SAH rats graded at 3-4 (our previously validated MRI grading scale) had larger T2 lesion volumes, more hydrocephalus and worse neurological function compared with those graded at 0-2. In conclusion, T2-lesion, WMI and hydrocephalus were the most prevalent MRI characteristics 24 hours after experimental SAH. The T2-lesion area matched with fibrinogen/fibrin positive staining in the acute phase of SAH. SAH induced more severe brain injury in females compared to males in the acute phase of SAH.

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Heme–Hemopexin Scavenging Is Active in the Brain and Associates With Outcome After Subarachnoid Hemorrhage

Cited by 51 publications

References 13 publications

Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic

Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic

Brain iron overload following intracranial haemorrhage

MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage

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