Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1

Schallner, Nils; Pandit, Rambhau; LeBlanc, Robert H.; Thomas, Ajith J.; Ogilvy, Christopher S.; Zuckerbraun, Brian S.; Gallo, David; Otterbein, Leo E.; Hanafy, Khalid A.

doi:10.1172/jci78443

Cited by 161 publications

(144 citation statements)

References 76 publications

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“…Usually HO-1 is considered as an oxidative stress protein in microglia and related to brain injury after ICH 11 . A recent study, however, indicated that HO-1 is associated with blood clearance by enhancing erythrophagocytosis after stroke 9 . In the current study, we found that the infiltration of CD163 and HO-1 positive cells into the hematoma increased with time paralleling hematoma resolution.…”

Section: Discussionmentioning

confidence: 94%

“…CD163 transports hemoglobin into microglia/macrophages with the subsequent induction of heme oxygenase-1 (HO-1) 8 . HO-1, a rate-limiting enzyme for heme degradation, is also considered as a modulator of erythrophagocytosis 9 . Deferoxamine (DFX), an iron chelator, reduces brain edema, white matter injury and neuronal cell death in rat and pig ICH models 10, 11 , and it also reduces clot lysis after ICH 12 .…”

Section: Introductionmentioning

confidence: 99%

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Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Cao

Zheng

Hua

et al. 2016

Stroke

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Background and Purpose Hematoma clearance occurs in the days after intracerebral hemorrhage (ICH) and has not been well studied. In the current study, we examined changes in the hematoma in a piglet ICH model. The effect of deferoxamine on hematoma was also examined. Methods The ICH model was induced by an injection of autologous blood into the right frontal lobe of piglets. First, a natural time course of hematoma changes up to 7 days was determined. Second, the effect of deferoxamine on hematoma changes was examined. Hemoglobin and membrane attack complex levels in the hematoma were examined by enzyme-linked immunosorbent assay. Immunohistochemistry and Western blotting was used to examine CD47 (a regulator of erythrophagocytosis), CD163 (a hemoglobin scavenger receptor) and heme oxygenase-1 (a heme degradation enzyme) in the clot. Results After ICH, there was a reduction in red blood cell diameter within the clot with time. This was accompanied by membrane attack complex accumulation and decreased hemoglobin levels. Erythrophagocytosis occurred in the hematoma and this was associated with reduced clot CD47 levels. Activated macrophages/microglia were CD163 and hemeoxygenase-1 positive and these accumulated in the clot with time. Deferoxamine treatment attenuated the process of hematoma resolution by reducing member attack complex formation and inhibiting CD47 loss in the clot. Conclusion These results indicate that membrane attack complex and erythrophagocytosis contribute to hematoma clearance after ICH, which can be altered by deferoxamine treatment.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Cao

Zheng

Hua

et al. 2016

Stroke

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“…Total RNA was extracted from 3 × 10 5 cells using TRIzol reagent (Thermo Scientific) and mRNA was reverse transcribed using an iScript cDNA Synthesis kit (Bio-Rad Laboratories) according to the manufacturer's instructions. Primer sequences of human AHR, HMOX1, and FOXP3 and of mouse Hmox1 and Cyp1A1 were as previously described (52)(53)(54)(55)(56). Human IL10 and ENTPD1 primer sequences were as follows: IL10 Forward 5′-TCCTTGCTGGAGGACTTTA-AGGGT-3′ and Reverse 5′-TGTCTGGGTCTTGGTTCTCAGCTT-3′; ENTPD1 Forward 5′-AGGT-GCCTATGGCTGGATTAC-3′ and Reverse 5′-CCAAAGCTCCAAAGGTTTCCT-3′.…”

Section: Quantitative Pcrmentioning

confidence: 99%

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

et al. 2017

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“…Thus, an early influx of leukocytes (particularly neutrophils) into the brain from the blood may exacerbate ischemic and hemorrhagic brain injury [125, 126], but a later inflammation may be beneficial in brain repair [127–129]. In the case of cerebral hemorrhage, infiltrating macrophages/resident microglia have an important role in hematoma resolution via phagocytosis [130, 131]. Infiltrating leukocytes may enter the brain across the BBB or the blood-CSF barrier after a stroke.…”

Section: Choroid Plexus As a Responder To Injurymentioning

confidence: 99%

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

Xiang

Routhe

Wilkinson

et al. 2017

Fluids Barriers CNS

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While the impact of hemorrhagic and ischemic strokes on the blood–brain barrier has been extensively studied, the impact of these types of stroke on the choroid plexus, site of the blood-CSF barrier, has received much less attention. The purpose of this review is to examine evidence of choroid plexus injury in clinical and preclinical studies of intraventricular hemorrhage, subarachnoid hemorrhage, intracerebral hemorrhage and ischemic stroke. It then discusses evidence that the choroid plexuses are important in the response to brain injury, with potential roles in limiting damage. The overall aim of the review is to highlight deficiencies in our knowledge on the impact of hemorrhagic and ischemic strokes on the choroid plexus, particularly with reference to intraventricular hemorrhage, and to suggest that a greater understanding of the response of the choroid plexus to stroke may open new avenues for brain protection.

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Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1

Cited by 161 publications

References 76 publications

Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Bilirubin suppresses Th17 immunity in colitis by upregulating CD39

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

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