Beneficial Role of Neutrophils Through Function of Lactoferrin After Intracerebral Hemorrhage

Zhao, Xiurong; Ting, Shun-Ming; Sun, Guanghua; Roy-O’Reilly, Meaghan; Mobley, Alexis S; Garrido, Jesus Bautista; Zheng, Xueping; Obertas, Lidiya; Jung, Jae-Chul; Kruzel, Marian L.; Aronowski, Jaroslaw

doi:10.1161/strokeaha.117.020544

Cited by 38 publications

(58 citation statements)

References 48 publications

(56 reference statements)

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“…Hematoma following ICH can directly compress brain tissue, which further induces mechanical damage and secondary brain injury [19,20,21]. In ammation contributes to brain damage following ICH, leading to macrophage activation and blood-brain barrier (BBB) disruption [22,23,24].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of TIPE2 attenuates macrophage activation and neuroinflammation after intracerebral hemorrhage in mice

Liu

Wang

et al. 2020

Preprint

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Background: Intracerebral hemorrhage (ICH) is a serious disease with high mortality and morbidity, and effective treatment is limited. A large amount of evidence suggests that the inflammatory response contributes to secondary brain damage following ICH. TIPE2 is an essential negative regulator of both innate and adaptive immunity, and depletion of TIPE2 causes inflammatory disease. However, the possible role of TIPE2 following ICH has not been reported. Methods: In this study, we investigated TIPE2 levels and inflammation in macrophages treated with erythrocyte lysate in vitro, and we observed proinflammatory cytokine production, BBB disruption, cerebral water content and neurological damage in ICH mice in vivo. Results: We found that TIPE2 levels were significantly decreased in erythrocyte lysate-treated macrophages compared to control macrophages. Upregulation of TIPE2 decreased macrophage activation and cytokine production and accelerated brain damage in ICH mice. In addition, upregulation of TIPE2 attenuated proinflammatory cytokine production, BBB disruption, and severe brain inflammation after ICH. Conclusion: The results demonstrated that TIPE2 was negatively correlated with the pathogenesis of ICH, which prevented brain injury and attenuated deleterious inflammatory responses following ICH. TIPE2 might serve as a novel target for ICH therapy.

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Section: Discussionmentioning

confidence: 99%

Upregulation of TIPE2 attenuates macrophage activation and neuroinflammation after intracerebral hemorrhage in mice

Liu

Wang

et al. 2020

Preprint

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“…7,25,26 However, inflammation has also been associated with brain recovery in the ICH setting. 7,27 Therefore, the role of inflammation in brain injury and recovery after ICH has not been completely defined.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoking History and Functional Outcomes After Spontaneous Intracerebral Hemorrhage

Chen

Ding

Ironside

et al. 2019

Stroke

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Background and Purpose: While cigarette use may be a risk for intracerebral hemorrhage (ICH), animal models suggest that nicotine has a potential neuroprotective effect. The aim of this multicenter study is to determine the effect of smoking history on outcome in ICH patients. Methods: We analyzed prospectively collected data from the Ethnic/Racial Variations of Intracerebral Hemorrhage study, and included patients with smoking status data in the analysis. Patients were dichotomized into non-smokers versus ever-smokers, and the latter group was further categorized as former (>30 days before ICH) or current (≤30 days before ICH) smokers. The primary outcome was 90-day modified Rankin Scale (mRS) score shift analysis. Secondary outcomes were in-hospital mortality and mortality, Barthel Index, and self-reported health status measures at 90 days. Results: The overall study cohort comprised 1,509 non-smokers and 1,423 ever-smokers (841 former, 577 current, 5 unknown). No difference in primary outcome was observed between nonsmokers versus ever-smokers (aOR=1.041 [0.904-1.199], p=0.577). No differences in primary outcome were observed between former (aOR=0.932 [0.791-1.178], p=0.399) or current smokers (aOR=1.178 [0.970-1.431], p=0.098) versus non-smokers. Subgroup analyses by race/ethnicity

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“…Thus, our results may provide another evidence for future statin use in ICH patients, and more related researches were needed to understand the potential mechanism. Interestingly, a recent work reported that systemic depletion of PMNs at 24 h after ICH exacerbated neurological deficits, suggesting that PMNs infiltration into the brain also shows some beneficial function at the subacute stage post-ICH (Zhao et al, 2018). After further investigation, they proposed that PMNs-mediated protective effect in subacute stage may through the two following ways: (1) PMNs can deliver cytoprotective lactoferrin to the ICH-affected brain, neutralizing iron and blocking its toxicity (Zhao et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a recent work reported that systemic depletion of PMNs at 24 h after ICH exacerbated neurological deficits, suggesting that PMNs infiltration into the brain also shows some beneficial function at the subacute stage post-ICH (Zhao et al, 2018). After further investigation, they proposed that PMNs-mediated protective effect in subacute stage may through the two following ways: (1) PMNs can deliver cytoprotective lactoferrin to the ICH-affected brain, neutralizing iron and blocking its toxicity (Zhao et al, 2018). (2) ICH can also transform the phenotype of PMNs that entering brain at the later stages, which then could enhance the beneficial effects like promoted blood detoxification efficacy (Zhao et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis

et al. 2018

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Statins, known for their lipid-lowering effects, also have immunomodulatory properties. This study aims to examine whether systematic simvastatin administration could decrease polymorphonuclear neutrophils (PMNs) infiltration into brain tissue, as well as alleviate neuroinflammation in a rat model of intracerebral hemorrhage (ICH). The ICH model was induced in adult male Sprague–Dawley rats by an injection of autologous blood. Animals randomly received simvastatin (i.p. 2 mg/kg) or vehicle daily from 5 days before ICH until sacrificed. Routine blood counts, brain water content, neurological scoring, immunofluorescence and RT-PCR were conducted to evaluate the anti-inflammatory effect of simvastatin following ICH. Furthermore, flow cytometric and western blotting analysis were implemented for elucidating the mechanisms involved in simvastatin-induced reduction of neutrophil brain-invading. Elevated PMNs count and neutrophil-to-lymphocyte ratio in circulation were detected in rat model of ICH, which was reversed by using simvastatin. Simvastatin effectively alleviated PMNs infiltration and proinflammatory factors release in perihematomal area, as well as attenuated ICH-induced brain edema and neurological deficits. Simvastatin significantly downregulated the expression of antiapoptotic protein-Mcl-1 while increased the level of proapoptotic protein-Bax and cleaved caspase 3 in PMNs. Simvastatin treatment significantly alleviated PMNs brain-infiltrating and subsequent neuroinflammatory reaction after ICH, in part by accelerating peripheral PMNs apoptosis through disorganized the expression of apoptotic related proteins. Our data provided new evidence for simvastatin application on patients with ICH.

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Beneficial Role of Neutrophils Through Function of Lactoferrin After Intracerebral Hemorrhage

Abstract: LTF delivered to the ICH-affected brain by infiltrating PMNs may assist in hematoma detoxification and represent a powerful potential target for the treatment of ICH.

Cited by 38 publications

References 48 publications

Upregulation of TIPE2 attenuates macrophage activation and neuroinflammation after intracerebral hemorrhage in mice

Upregulation of TIPE2 attenuates macrophage activation and neuroinflammation after intracerebral hemorrhage in mice

Cigarette Smoking History and Functional Outcomes After Spontaneous Intracerebral Hemorrhage

Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis

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