ArticleDisease models & mechanisms2012
Interleukin-1 receptor antagonist is beneficial after subarachnoid haemorrhage in rat by blocking haem-driven inflammatory pathology.
Article in Disease models & mechanisms, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Haptoglobin Genotype and Outcome after Subarachnoid Haemorrhage: New Insights from a Meta-Analysis.Oxidative medicine and cellular longevity · 2017Pooled it
- Clinical review: Brain-body temperature differences in adults with severe traumatic brain injury.Critical care (London, England) · 2013Pooled it
- Effects of stellate ganglion block on early brain injury in patients with subarachnoid hemorrhage: a randomised control trial.BMC anesthesiology · 2021Trial
- Intraventricular fibrinolysis with tissue plasminogen activator is associated with transient cerebrospinal fluid inflammation: a randomized controlled trial.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Trial
- Plasma Biomarkers of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.Brain sciences · 2026Article
- Olfactory mucosa mesenchymal stem cell-derived exosomes protect against neuroinflammation after subarachnoid hemorrhage by activating mitophagy.The Kaohsiung journal of medical sciences · 2025Article
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
- The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model.Medicina (Kaunas, Lithuania) · 2024Article
- Article
- Emerging Treatments for Subarachnoid Hemorrhage.CNS & neurological disorders drug targets · 2024Review
- Animal Welfare Aspects in Planning and Conducting Experiments on Rodent Models of Subarachnoid Hemorrhage.Cellular and molecular neurobiology · 2023Review
- Clinical Potential of Immunotherapies in Subarachnoid Hemorrhage Treatment: Mechanistic Dissection of Innate and Adaptive Immune Responses.Aging and disease · 2023Review
- Early Brain Injury and Neuroprotective Treatment after Aneurysmal Subarachnoid Hemorrhage: A Literature Review.Brain sciences · 2023Review
- Systemic Inflammation after Aneurysmal Subarachnoid Hemorrhage.International journal of molecular sciences · 2023Review
- Systemic innate myeloid responses to acute ischaemic and haemorrhagic stroke.Seminars in immunopathology · 2023Review
- The Role of Circadian Clock Genes in Critical Illness: The Potential Role of Translational Clock Gene Therapies for Targeting Inflammation, Mitochondrial Function, and Muscle Mass in Intensive Care.Journal of biological rhythms · 2022Review
- Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update.Stem cell research & therapy · 2022Review
- The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.Fluids and barriers of the CNS · 2022Review
- Necrotic reshaping of the glioma microenvironment drives disease progression.Acta neuropathologica · 2022Review
- Immune response treated with bone marrow mesenchymal stromal cells after stroke.Frontiers in neurology · 2022Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Subarachnoid haemorrhage (SAH) is a major contributor to the burden of stroke on society. Treatment options are limited and animal models of SAH do not always mimic key pathophysiological hallmarks of the disease, thus hindering development of new therapeutics. Inflammation is strongly associated with brain injury after SAH in animals and patients, and inhibition of the pro-inflammatory cytokine interleukin-1 (IL-1) represents a possible therapeutic target. Here we report that a rupture of the middle cerebral artery in the rat produces heterogeneous infarct patterns similar to those observed in human SAH. Administration of the IL-1 receptor antagonist (IL-1Ra) reduced blood-brain barrier breakdown, and the extent of breakdown correlated with brain injury. After SAH, haem oxygenase-1 (HO-1) was strongly expressed around the bleed site and in the cortex and striatum, indicating the presence of free haem, a breakdown product of haemoglobin. HO-1 expression was also found in the same regions as microglial/macrophage expression of IL-1α. The direct effect of haem on IL-1α expression was confirmed in vitro using organotypic slice culture (OSC). Haem-induced cell death was dependent on IL-1 signalling, with IL-1Ra completely blocking cellular injury. Furthermore, stimulation of mouse primary mixed glial cells with haem induced the release of IL-1α, but not IL-1β. Thus, we suggest that haem, released from lysed red blood cells (RBCs) in the subarachnoid space, acts as a danger-associated molecular pattern (DAMP) driving IL-1-dependent inflammation. These data provide new insights into inflammation after SAH-induced brain injury and suggest IL-1Ra as a candidate therapeutic for the disease.
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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.