ArticleJournal of neuroinflammation2021
Cell-free oxidized hemoglobin drives reactive oxygen species production and pro-inflammation in an immature primary rat mixed glial cell culture.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Exendin-4 improves neurodevelopmental outcome after neonatal germinal matrix hemorrhage.Cell death & disease · 2026Article
- Exploring hemoglobin dynamics and scavenging mechanisms in preterm infants and preterm rabbits with cerebral intraventricular hemorrhage.Pediatric research · 2026Article
- Acellular Hemoglobin Impairs Cardiomyocyte Excitation-Contraction Coupling.ASAIO journal (American Society for Artificial Internal Organs : 1992) · 2026Article
- Feasibility Study on Inflammasome Proteins as Biomarkers in the Cerebrospinal Fluid of Pediatric Patients with Hydrocephalus Due to Intraventricular Hemorrhage.Biomolecules · 2025Article
- Unraveling the Mystery of Hemoglobin in Hypoxia-Accelerated Neurodegenerative Diseases.Biomolecules · 2025Review
- Hemoglobin as a pseudoperoxidase and drug target for oxidative stress-related diseases.Signal transduction and targeted therapy · 2025Article
- Serum-free endothelial cell culture medium for vascular smooth muscle cells sheet formation.Journal of biological engineering · 2025Article
- Free heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4/MyD88/NF-κB signaling pathway.Cell communication and signaling : CCS · 2024Article
- Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention.Frontiers in molecular neuroscience · 2024Review
- Ascorbate protects human kidney organoids from damage induced by cell-free hemoglobin.Disease models & mechanisms · 2023Article
- Ginsenoside ompound K reduces neuronal damage and improves neuronal synaptic dysfunction by targeting Aβ.Frontiers in pharmacology · 2023Article
- Extracellular Hemoglobin: Modulation of Cellular Functions and Pathophysiological Effects.Biomolecules · 2022Review
- Novel aspects of sepsis pathophysiology: NETs, plasma glycoproteins, endotheliopathy and COVID-19.Journal of pharmacological sciences · 2022Review
- The relationship between hemoglobin and triglycerides in moyamoya disease: A cross-sectional study.Frontiers in neurology · 2022Article
- The Oxidative Injury of Extracellular Hemoglobin Is Associated With Reactive Oxygen Species Generation of Grass Carp (Frontiers in immunology · 2022Article
- The Toxic Influence of Excess Free Iron on Red Blood Cells in the Biophysical Experiment: An In Vitro Study.Journal of toxicology · 2022Article
- Cerebellar development after preterm birth.Frontiers in cell and developmental biology · 2022Review
- Hemoglobin induces inflammation through NF-kB signaling pathway and causes cell oxidative damage in grass carp (Frontiers in immunology · 2022Article
- Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells.International journal of molecular sciences · 2021Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundGerminal matrix intraventricular hemorrhage (GM-IVH) is associated with deposition of redox active cell-free hemoglobin (Hb), derived from hemorrhagic cerebrospinal fluid (CSF), in the cerebrum and cerebellum. In a recent study, using a preterm rabbit pup model of IVH, intraventricularly administered haptoglobin (Hp), a cell-free Hb scavenger, partially reversed the damaging effects observed following IVH. Together, this suggests that cell-free Hb is central in the pathophysiology of the injury to the immature brain following GM-IVH. An increased understanding of the causal pathways and metabolites involved in eliciting the damaging response following hemorrhage is essential for the continued development and implementation of neuroprotective treatments of GM-IVH in preterm infant.
methodsWe exposed immature primary rat mixed glial cells to hemorrhagic CSF obtained from preterm human infants with IVH (containing a mixture of Hb-metabolites) or to a range of pure Hb-metabolites, incl. oxidized Hb (mainly metHb with iron in Fe
resultsExposure of the glial cells to hemorrhagic CSF as well as oxidized Hb, but not oxyHb, resulted in a significantly increased rate of ROS production that positively correlated with the rate of production of pro-inflammatory and oxidative markers. Congruently, exposure to oxidized Hb caused a disintegration of the polygonal cytoskeletal structure of the glial cells in addition to upregulation of F-actin proteins in microglial cells. Co-administration of Hp partially reversed the damaging response of hemorrhagic CSF and oxidized Hb.
conclusionExposure of mixed glial cells to oxidized Hb initiates a pro-inflammatory and oxidative response with cytoskeletal disintegration. Early administration of Hp, aiming to minimize the spontaneous autoxidation of cell-free oxyHb and liberation of heme, may provide a therapeutic benefit in preterm infant with GM-IVH.
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