ArticleStroke2013
Mitigation of murine focal cerebral ischemia by the hypocretin/orexin system is associated with reduced inflammation.
Article in Stroke, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- The neuropeptide in ischemic brain injury: insights, challenges, and horizon of targeted interventions.Journal of translational medicine · 2026Pooled it
- Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder.Annals of medicine · 2026Article
- Dual orexin receptor antagonism with lemborexant enhances microglial clearance of β-amyloid in mice.Molecular neurodegeneration · 2026Article
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- Awakening Recovery: Enhancing Orexinergic Tone After Acute CNS Damage.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lemborexant Reduces Infarct Volume and Improves Long-Term Functional Recovery in a Murine Model of Ischemic Stroke.bioRxiv : the preprint server for biology · 2025Article
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- The orexin/hypocretin system in dementia-related neurological disorders: a double-edged sword in cognitive impairment.Psychopharmacology · 2025Review
- Neuroprotective Effects of Transcranial Pulsed Current Stimulation: Modulation of Microglial Polarization in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2025Article
- Orexin/Hypocretin Modulates Neuroinflammatory Response to LPS in a Sex and Brain-Region Specific Manner in Young Rats.Journal of neurochemistry · 2025Article
- The interaction between orexin, sleep deprivation and Alzheimer's disease: Unveiling an Emerging Connection.The journal of physiological sciences : JPS · 2025Review
- The Orexin System and Its Impact on the Autonomic Nervous and Cardiometabolic System in Post-Acute Sequelae of COVID-19.Biomedicines · 2025Review
- Opioid-induced neuroanatomical, microglial and behavioral changes are blocked by suvorexant without diminishing opioid analgesia.Nature. Mental health · 2024Article
- Therapeutic effects of orexin-A in sepsis-associated encephalopathy in mice.Journal of neuroinflammation · 2024Article
- Deciphering Post-Stroke Sleep Disorders: Unveiling Neurological Mechanisms in the Realm of Brain Science.Brain sciences · 2024Review
- Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis.Scientific reports · 2024Article
- Locomotor activity as an effective measure of the severity of inflammatory arthritis in a mouse model.PloS one · 2024Article
- Inclusion of hypocretin-1 improved performance of poor sleep quality prediction for elderly patients with acute ischemic stroke: a prospective cohort study.Frontiers in aging neuroscience · 2024Article
- Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Cognitive Impairment and Intestinal Microecological Dysfunction Induced by High-Fat Diet in Rats.Research (Washington, D.C.) · 2024Article
- [Investigation of the mechanism of action and identification of candidate traditional Chinese medicines for the treatment of ischemic stroke in the Danshen-Jiangxiang pair based on drug-target-disease association network].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeBrain ischemia causes immediate and delayed cell death that is exacerbated by inflammation. Recent studies show that hypocretin-1/orexin-A (Hcrt-1) reduces ischemic brain injury, and Hcrt-positive neurons modulate infection-induced inflammation. Here, we tested the hypothesis that Hcrt plays a protective role against ischemia by modulating inflammation.
methodsOrexin/ataxin-3 (AT) mice, a transgenic strain in which Hcrt-producing neurons degenerate in early adulthood, and wild-type mice were subjected to transient middle cerebral artery occlusion (MCAO). Infarct volume, neurological score, and spontaneous home cage activity were assessed. Inflammation was measured using immunohistochemistry, ELISA, and assessment of cytokine mRNA levels.
resultsInfarct volumes 24 and 48 hours after MCAO were significantly larger, neurological score was worse, and spontaneous activity decreased in AT compared with wild-type mice. Macrophage/microglial infiltration and myeloperoxidase-positive cells were higher in AT compared with wild-type mice. Pre-MCAO intracerebroventricular injection of Hcrt-1 significantly reduced infarct volume and macrophage/microglial infiltration in both genotypes and improved neurological score in AT mice. Post-MCAO treatment decreased infarct size in both wild-type and AT mice, but had no effect on neurological score in either genotype. Microglia express the Hcrt-1 receptor after MCAO. Tumor necrosis factor-α production by lipopolysaccharide-stimulated microglial BV2 cells was significantly reduced by Hcrt-1 pretreatment. Sham AT mice exhibit increased brain tumor necrosis factor-α and interleukin-6 mRNA, suggesting chronic inflammation.
conclusionsLoss of Hcrt neurons in AT mice resulted in worsened stroke outcomes, which were reversed by administration of exogenous Hcrt-1. The mechanism underlying Hcrt-mediated neuroprotection includes attenuation of inflammatory responses after ischemic insult.
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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.