Neutrophil extracellular traps: A novel therapeutic target for intracranial hemorrhage

Jin, Jiaqi; Zhao, Xinyi; Li, Wenqiang; Wang, Fang; Tian, Jiawei; Wang, Nan; Gao, Xin; Zhang, Jiheng; Wu, Jiasheng; Mang, Ge; Ma, Ruishuang; Hu, Shaoshan

doi:10.1016/j.thromres.2022.08.024

Cited by 9 publications

(2 citation statements)

References 61 publications

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“…These NETs are composed of extracellular DNA fibers that are decorated with histones and granular proteins 32 . This discovery supports prior research that has also shown the presence of NETs in similar cases 33 . Further, our data indicate that an increased presence of neutrophils in the peripheral blood of these patients is inversely proportional to the GOS score at discharge, pointing toward a poorer prognosis with a higher neutrophil count.…”

Section: Discussionsupporting

confidence: 90%

“…32 This discovery supports prior research that has also shown the presence of NETs in similar cases. 33 Further, our data indicate that an increased presence of neutrophils in the peripheral blood of these patients is inversely proportional to the GOS score at discharge, pointing toward a poorer prognosis with a higher neutrophil count. Extending our investigations to ascertain the presence of NETs in brain tissue, we established a rat model of ICH.…”

Section: Discussionmentioning

confidence: 50%

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Integrating network pharmacology and transcriptomic omics reveals that akebia saponin D attenuates neutrophil extracellular traps‐induced neuroinflammation via NTSR1/PKAc/PAD4 pathway after intracerebral hemorrhage

Gu,

Ye,

Chen

et al. 2023

The FASEB Journal

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Neutrophils and their production of neutrophil extracellular traps (NETs) significantly contribute to neuroinflammation and brain damage after intracerebral hemorrhage (ICH). Although Akebia saponin D (ASD) demonstrates strong anti‐inflammatory activities and blood–brain barrier permeability, its role in regulating NETs formation and neuroinflammation following ICH is uncharted. Our research focused on unraveling the influence of ASD on neuroinflammation mediated by NETs and the mechanisms involved. We found that increased levels of peripheral blood neutrophils post‐ICH are correlated with worse prognostic outcomes. Through network pharmacology, we identified ASD as a promising therapeutic target for ICH. ASD administration significantly improved neurobehavioral performance and decreased NETs production in neutrophils. Furthermore, ASD was shown to upregulate the membrane protein NTSR1 and activate the cAMP signaling pathway, confirmed through transcriptome sequencing, western blot, and immunofluorescence. Interestingly, the NTSR1 inhibitor SR48692 significantly nullified ASD's anti‐NETs effects and dampened cAMP pathway activation. Mechanistically, suppression of PKAc via H89 negated ASD's anti‐NETs effects but did not affect NTSR1. Our study suggests that ASD may reduce NETs formation and neuroinflammation, potentially involving the NTSR1/PKAc/PAD4 pathway post‐ICH, underlining the potential of ASD in mitigating neuroinflammation through its anti‐NETs properties.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 50%