ArticleTranslational stroke research2012
Heparin reduces neuroinflammation and transsynaptic neuronal apoptosis in a model of subarachnoid hemorrhage.
Article in Translational stroke research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04507178 (Improving Outcome in Subarachnoid Hemorrhage wIth Nadroparine), which is not on this map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Improving Outcome in Subarachnoid Hemorrhage wIth Nadroparine
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An "Heparin Oriented" Systematic Review.International journal of molecular sciences · 2023Pooled it
- Microthrombi and hypercoagulability's contribution to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Improving outcome in SubaraChnoid HEMorrhage wIth nAdroparin (ISCHEMIA): a prospective randomised controlled trial protocol.BMJ open · 2025Article
- Pharmacotherapy in SAH: Clinical Trial Lessons.CNS & neurological disorders drug targets · 2024Review
- Myelin sheath injury and repairment after subarachnoid hemorrhage.Frontiers in pharmacology · 2023Review
- Microglial TLR4 is Critical for Neuronal Injury and Cognitive Dysfunction in Subarachnoid Hemorrhage.Neurocritical care · 2022Article
- Article
- Diffusion-weighted imaging-positive lesions following endovascular treatment for ruptured and unruptured aneurysms: Its incidence according to antithrombotic drugs.Journal of cerebrovascular and endovascular neurosurgery · 2022Article
- The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.Fluids and barriers of the CNS · 2022Review
- Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review.Journal of the American Heart Association · 2021Review
- The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke.Translational stroke research · 2021Review
- The Structure and Function of the Glycocalyx and Its Connection With Blood-Brain Barrier.Frontiers in cellular neuroscience · 2021Review
- Hippocampal Transcriptome Changes After Subarachnoid Hemorrhage in Mice.Frontiers in neurology · 2021Article
- The Role of Heparin and Glycocalyx in Blood-Brain Barrier Dysfunction.Frontiers in immunology · 2021Review
- Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Neuroinflammation and Microvascular Dysfunction After Experimental Subarachnoid Hemorrhage: Emerging Components of Early Brain Injury Related to Outcome.Neurocritical care · 2019Review
- Effects of pumpless extracorporeal lung assist on hemodynamics, gas exchange and inflammatory cascade response during experimental lung injury.Experimental and therapeutic medicine · 2018Article
- Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?Frontiers in neurology · 2018Review
- Expression of caspase-3, Bax and Bcl-2 in hippocampus of rats with diabetes and subarachnoid hemorrhage.Experimental and therapeutic medicine · 2018Article
- Heparin and Heparin-Derivatives in Post-Subarachnoid Hemorrhage Brain Injury: A Multimodal Therapy for a Multimodal Disease.Molecules (Basel, Switzerland) · 2017Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Subarachnoid hemorrhage (SAH) can lead to disabling motor, cognitive, and neuropsychological abnormalities. Part of the secondary injury to cerebral tissues associated with SAH is attributable to the neuroinflammatory response induced by blood. Heparin is a pleiotropic compound that reduces inflammatory responses in conditions outside the central nervous system. Using a model of SAH devoid of global insult, we evaluated the effect of delayed intravenous (IV) infusion of heparin, at a dose that does not produce therapeutic anticoagulation, on neuroinflammation, myelin preservation, and apoptosis. Adult male rats underwent bilateral stereotactic injections of autologous blood (50 μL) into the subarachnoid space of the entorhinal cortex. The rats were implanted with mini-osmotic pumps that delivered either vehicle or unfractionated heparin (10 U/kg/h IV) beginning 12 h after SAH. No mechanical or hemorrhagic injury was observed in the hippocampus. In vehicle controls assessed at 48 h, SAH was associated with robust neuroinflammation in the adjacent cortex [neutrophils, activated phagocytic microglia, nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-1beta] and neurodegeneration (Fluoro-Jade C staining and loss of NeuN). In the hippocampus, a muted neuroinflammatory response was indicated by Iba1-positive, ED1-negative microglia exhibiting an activated morphology. The perforant pathway showed Fluoro-Jade C staining and demyelination, and granule cells of the dentate gyrus had pyknotic nuclei, labeled with Fluoro-Jade C and showed upregulation of cleaved caspase-3, consistent with transsynaptic apoptosis. Administration of heparin significantly reduced neuroinflammation, demyelination, and transsynaptic apoptosis. We conclude that delayed IV infusion of low-dose unfractionated heparin may attenuate adverse neuroinflammatory effects of SAH.
Identifiers
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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.