ArticleEMBO molecular medicine2024
Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review.Open veterinary journal · 2026Pooled it
- Microglial Mitochondrial Dysfunction: The Storm Center of Post-Stroke Neuroinflammation.CNS neuroscience & therapeutics · 2026Review
- Colchicine as an Adjunctive Therapy to Improve Ischemic Stroke Reperfusion Outcomes in Mice.CNS neuroscience & therapeutics · 2026Article
- Advances in genetics and multi-omics for ischemic stroke: from pathogenesis to clinical translation.Frontiers in genetics · 2026Review
- From Electron Imbalance to Network Collapse: Decoding the Redox Code of Ischemic Stroke for Biomarker-Guided Precision Neuroprotection.International journal of molecular sciences · 2025Review
- Inhibition Effects and Mechanism Study of rAj-HRP30, a Recombinant Histidine-Rich Peptide fromInternational journal of molecular sciences · 2025Article
- Early identification and integrated nursing management of post-thrombolysis hemorrhagic transformation in acute ischemic stroke: a comprehensive review.Frontiers in neurology · 2025Review
- Predictive Value of the Modified Comprehensive Immunoinflammatory Indices for Hemorrhagic Transformation in Ischemic Stroke Patients Undergoing Thrombolysis: A Retrospective Study.International journal of general medicine · 2025Article
- Bioactive Materials Facilitate the Restoration of Neurological Function Post Cerebral Ischemic Stroke.International journal of nanomedicine · 2024Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.
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