ArticleThe Journal of clinical investigation2015
Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 216 citations in OpenAlex.
- A Systematic Review of Inflammatory Cytokine Changes Following Aneurysmal Subarachnoid Hemorrhage in Animal Models and Humans.Translational stroke research · 2022Pooled it
- A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.Translational stroke research · 2017Pooled it
- EGCG-loaded nanoparticles attenuate post-SAH white matter injury by targeting HO-1/S100A10 to suppress oxidative stress-induced reactive astrocytes.Redox report : communications in free radical research · 2026Article
- Toll like receptor 4 (TLR4) in neuroinflammation: From acute hemorrhagic stroke to chronic neurodegeneration.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.Journal of neuroinflammation · 2026Review
- The Role of Cold-Inducible RNA-Binding Protein (CIRP) in Neurological Disorders.Brain sciences · 2026Review
- The senescent niche hypothesis: microglial dysfunction and replacement strategies in drug-resistant epilepsy.Frontiers in immunology · 2026Review
- Cerebrospinal Fluid Erythrocyte Burden Amplifies the Impact of PTAU on Entorhinal Degeneration in Alzheimer's Disease.Biomolecules · 2025Article
- Erythrocyte Load in Cerebrospinal Fluid Linked with Hippocampal Atrophy in Alzheimer's Disease.Journal of clinical medicine · 2025Article
- Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide.Medicinal research reviews · 2025Review
- Development of a 3D Brain Model to Study Sex-Specific Neuroinflammation After Hemorrhagic Stroke.Translational stroke research · 2025Article
- Optimization and evaluation of an experimental subarachnoid hemorrhage model in mice.Scientific reports · 2025Article
- Macrophage Lyn Kinase Is a Sex-Specific Regulator of Post-Subarachnoid Hemorrhage Neuroinflammation.Journal of the American Heart Association · 2025Article
- Curcumin Alleviates Microglia-Mediated Neuroinflammation and Neuronal Ferroptosis Following Experimental Subarachnoid Hemorrhage by Modulating the Nrf2/HO-1 Signaling Pathway.Molecular neurobiology · 2025Article
- All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
- The sentinel against brain injury post-subarachnoid hemorrhage: efferocytosis of erythrocytes by leptomeningeal lymphatic endothelial cells.Theranostics · 2025Article
- Severity of Repetitive Mild Traumatic Brain Injury Depends on Microglial Heme Oxygenase-1 and Carbon Monoxide.The European journal of neuroscience · 2025Article
- Sirtuins as Potential Targets for Neuroprotection: Mechanisms of Early Brain Injury Induced by Subarachnoid Hemorrhage.Translational stroke research · 2024Review
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Subarachnoid hemorrhage (SAH) carries a 50% mortality rate. The extravasated erythrocytes that surround the brain contain heme, which, when released from damaged red blood cells, functions as a potent danger molecule that induces sterile tissue injury and organ dysfunction. Free heme is metabolized by heme oxygenase (HO), resulting in the generation of carbon monoxide (CO), a bioactive gas with potent immunomodulatory capabilities. Here, using a murine model of SAH, we demonstrated that expression of the inducible HO isoform (HO-1, encoded by Hmox1) in microglia is necessary to attenuate neuronal cell death, vasospasm, impaired cognitive function, and clearance of cerebral blood burden. Initiation of CO inhalation after SAH rescued the absence of microglial HO-1 and reduced injury by enhancing erythrophagocytosis. Evaluation of correlative human data revealed that patients with SAH have markedly higher HO-1 activity in cerebrospinal fluid (CSF) compared with that in patients with unruptured cerebral aneurysms. Furthermore, cisternal hematoma volume correlated with HO-1 activity and cytokine expression in the CSF of these patients. Collectively, we found that microglial HO-1 and the generation of CO are essential for effective elimination of blood and heme after SAH that otherwise leads to neuronal injury and cognitive dysfunction. Administration of CO may have potential as a therapeutic modality in patients with ruptured cerebral aneurysms.
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What OpenQuestion holds
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.