A Review of Hematoma Components Clearance Mechanism After Subarachnoid Hemorrhage

Pan, Pengjie; Xu, Li; Zhang, Hongrong; Liu, Yuan; Lu, Xiaocheng; Chen, Gang; Tang, Hailiang; Wu, Jiang

doi:10.3389/fnins.2020.00685

Cited by 33 publications

(32 citation statements)

References 95 publications

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“…4 As a result, early brain injury (EBI), which consists of neuronal apoptosis, impaired autoregulation, brain edema, cortical spreading depression (CSD) and microcirculatory dysfunction, has become a focus of interest. 5–12…”

Section: Introductionmentioning

confidence: 99%

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage

Naraoka

Matsuda

Shimamura

et al. 2021

J Cereb Blood Flow Metab

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Early brain injury (EBI) is considered an important cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). As a factor in EBI, microcirculatory dysfunction has become a focus of interest, but whether microcirculatory dysfunction is more important than angiographic vasospasm (aVS) remains unclear. Using data from 128 cases, we measured the time to peak (TTP) in several regions of interest on digital subtraction angiography. The intracerebral circulation time (iCCT) was obtained between the TTP in the ultra-early phase (the baseline iCCT) and in the subacute phase and/or at delayed cerebral ischemia (DCI) onset (the follow-up iCCT). In addition, the difference in the iCCT was calculated by subtracting the baseline iCCT from the follow-up iCCT. Univariate analysis showed that DCI was significantly increased in those patients with a prolonged baseline iCCT, prolonged follow-up iCCT, increased differences in the iCCT, and with severe aVS. Poor outcome was significantly increased in patients with prolonged follow-up iCCT and increased differences in the iCCT. Multivariate analysis revealed that increased differences in the iCCT were a significant risk factor that increased DCI and poor outcome. The results suggest that the increasing microcirculatory dysfunction over time, not aVS, causes DCI and poor outcome after aneurysmal aSAH.

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Section: Introductionmentioning

confidence: 99%

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage

Naraoka

Matsuda

Shimamura

et al. 2021

J Cereb Blood Flow Metab

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“…These results show that brain endothelial erythrophagocytosis is associated with an increase in abluminal (brain facing) iron load. Once in the brain parenchyma, microglial cells are well equipped to clear RBC and its degradation products, including hemoglobin, via scavenger receptors including CD36, CD47, CD163, and CD91 ( Pan et al, 2020 ). Within the microglial cells, hemoglobin can be broken down into free heme followed by free iron that is stored as the insoluble hemosiderin-iron.…”

Section: Discussionmentioning

confidence: 99%

Insights Into the Mechanisms of Brain Endothelial Erythrophagocytosis

Sun

Vyas

Mann

et al. 2021

Front. Cell Dev. Biol.

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The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 cells) were incubated with tert-butyl hydroperoxide (tBHP, oxidative stressor to induce RBC aging in vitro)- or PBS (control)-treated mouse RBCs. tBHP increased the reactive oxygen species (ROS) formation and phosphatidylserine exposure in RBCs, which were associated with robust brain endothelial erythrophagocytosis. TNFα treatment potentiated the brain endothelial erythrophagocytosis of tBHP-RBCs in vitro. Brain endothelial erythrophagocytosis was significantly reduced by RBC phosphatidylserine cloaking with annexin-V and with RBC-ROS and phosphatidylserine reduction with vitamin C. Brain endothelial erythrophagocytosis did not alter the bEnd.3 viability, and tBHP-RBCs were localized with early and late endosomes. Brain endothelial erythrophagocytosis increased the bEnd.3 total iron pool, abluminal iron levels without causing brain endothelial monolayer disruption, and ferroportin levels. In vivo, intravenous tBHP-RBC injection in aged (17–18 months old) male C57BL/6 mice significantly increased the Prussian blue-positive iron-rich lesion load compared with PBS-RBC-injected mice. In conclusion, RBC phosphatidylserine exposure and ROS are key mediators of brain endothelial erythrophagocytosis, a process which is associated with increased abluminal iron in vitro. tBHP-RBCs result in Prussian blue-positive iron-rich lesions in vivo. Brain endothelial erythrophagocytosis may provide a new route for RBC/RBC degradation product entry into the brain to produce iron-rich cerebral microhemorrhage-like lesions.

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“…Hemoglobin can be engulfed by cells in three ways: erythrophagocytosis, endocytosis of erythrocytes mediated by haptoglobin, and endocytosis of heme mediated by hemopexin (Figure 7; Bulters et al, 2018;Pan et al, 2020). These mechanisms of endogenous hemoglobin clearance provide an entry point for therapeutic regimens that target hemoglobin.…”

Section: Enhancing Endogenous Hemoglobin Clearancementioning

confidence: 99%

Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage

Liu

et al. 2021

Front. Cell. Neurosci.

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Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body of evidence suggests that neuroinflammation and oxidative stress play a negative role in neurofunctional deficits. Red blood cells and hemoglobin, immune cells, proinflammatory cytokines, and peroxidases are directly or indirectly involved in the regulation of neuroinflammation and oxidative stress in the central nervous system after SAH. This review explores the role of various cellular and acellular components in secondary inflammation and oxidative stress after SAH, and aims to provide new ideas for clinical treatment to improve the prognosis of SAH.

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A Review of Hematoma Components Clearance Mechanism After Subarachnoid Hemorrhage

Cited by 33 publications

References 95 publications

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage

Insights Into the Mechanisms of Brain Endothelial Erythrophagocytosis

Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage

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