ArticleThe Journal of clinical investigation2019
Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses 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
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An "Heparin Oriented" Systematic Review.International journal of molecular sciences · 2023Pooled it
- Meta-analysis of associations of genetic polymorphisms with cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.Acta neurologica Belgica · 2022Pooled it
- Comparative Analysis of CSF Drainage from Lumbar and External Ventricular Drains in Aneurysmal Subarachnoid Hemorrhage.Neurocritical care · 2026Article
- Hemoglobin binders reduce inflammation and tissue injury from hemolysis in venovenous extracorporeal circulation.Blood advances · 2026Article
- Haptoglobin and Hemopexin Redirect Heme-Driven Oxidative Stress and Neurotoxicity in Organotypic Brain Slices.ACS chemical neuroscience · 2026Article
- Bioinformatics Analysis of ZDHHC-protein Acyltransferase for Predicting the Rupture of Aneurysmal Subarachnoid Hemorrhage.Current neurovascular research · 2026Article
- Imaging efficacy and safety of low dose intraventricular tissue plasminogen activator in aneurysmal subarachnoid hemorrhage: case series.Acta neurochirurgica · 2025Article
- Iron Hemostasis in Patients With Subarachnoid Hemorrhage and the Role of Early CSF Drainage.Neurology · 2025Review
- Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep.Translational stroke research · 2025Article
- Scavenger endothelial cells alleviate tissue damage by engulfing toxic molecules derived from hemolysis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Similarities in the Electrographic Patterns of Delayed Cerebral Infarction and Brain Death After Aneurysmal and Traumatic Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- Red Blood Cells in the Cerebrospinal Fluid Compartment After Subarachnoid Haemorrhage: Significance and Emerging Therapeutic Strategies.Translational stroke research · 2025Review
- All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- Cerebrospinal fluid haptoglobin levels and outcome after aneurysmal subarachnoid haemorrhage: Evidence from Mendelian randomization.PloS one · 2025Article
- Deciphering the role of miRNA-mRNA interactions in cerebral vasospasm post intracranial hemorrhage.Frontiers in molecular biosciences · 2025Article
- Article
- The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice.Nature communications · 2024Article
- Iron Accumulation and Metabolic Alterations in Aneurysmal Subarachnoid Hemorrhage.Stroke (Hoboken, N.J.) · 2024Article
- OxyHbMeter-a novel bedside medical device for monitoring cell-free hemoglobin in the cerebrospinal fluid-proof of principle.Frontiers in medical technology · 2024Article
- The Haptoglobin Response after Aneurysmal Subarachnoid Haemorrhage.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delayed ischemic neurological deficit (DIND) is a major driver of adverse outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH), defining an unmet need for therapeutic development. Cell-free hemoglobin that is released from erythrocytes into the cerebrospinal fluid (CSF) is suggested to cause vasoconstriction and neuronal toxicity, and correlates with the occurrence of DIND. Cell-free hemoglobin in the CSF of patients with aSAH disrupted dilatory NO signaling ex vivo in cerebral arteries, which shifted vascular tone balance from dilation to constriction. We found that selective removal of hemoglobin from patient CSF with a haptoglobin-affinity column or its sequestration in a soluble hemoglobin-haptoglobin complex was sufficient to restore physiological vascular responses. In a sheep model, administration of haptoglobin into the CSF inhibited hemoglobin-induced cerebral vasospasm and preserved vascular NO signaling. We identified 2 pathways of hemoglobin delocalization from CSF into the brain parenchyma and into the NO-sensitive compartment of small cerebral arteries. Both pathways were critical for hemoglobin toxicity and were interrupted by the large hemoglobin-haptoglobin complex that inhibited spatial requirements for hemoglobin reactions with NO in tissues. Collectively, our data show that compartmentalization of hemoglobin by haptoglobin provides a novel framework for innovation aimed at reducing hemoglobin-driven neurological damage after subarachnoid bleeding.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.