ArticleBrain, behavior, and immunity2015
(+)-Naltrexone is neuroprotective and promotes alternative activation in the mouse hippocampus after cardiac arrest/cardiopulmonary resuscitation.
Article in Brain, behavior, and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Low-dose naltrexone as an adjunctive treatment for major depressive disorder: findings from a randomized, double-blind, placebo-controlled hybrid parallel-arm study.Frontiers in pharmacology · 2026Trial
- Effect of Nalmefene on Delayed Neurocognitive Recovery in Elderly Patients Undergoing Video-assisted Thoracic Surgery with One Lung Ventilation.Current medical science · 2020Trial
- Sodium butyrate attenuates microglia-mediated neuroinflammation by modulating the TLR4/MyD88/NF-κB pathway and microbiome-gut-brain axis in cardiac arrest mice.Molecular brain · 2025Article
- The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Acute Low Dose Naltrexone Increases β-Endorphin and Promotes Neuronal Recovery Following Hypoxia-Ischemic Stroke in Type-2 Diabetic Mice.Neurochemical research · 2023Article
- Flufenamic acid improves survival and neurologic outcome after successful cardiopulmonary resuscitation in mice.Journal of neuroinflammation · 2022Article
- Systemic administration of dendrimer N-acetyl cysteine improves outcomes and survival following cardiac arrest.Bioengineering & translational medicine · 2022Article
- Immunometabolic Modulatory Role of Naltrexone in BV-2 Microglia Cells.International journal of molecular sciences · 2021Article
- Saccharin and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: role of BDNF and enkephalin.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Opioid Antagonist in the Treatment of Ischemic Stroke.Brain sciences · 2021Review
- Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Topical Therapeutic Options in Corneal Neuropathic Pain.Frontiers in pharmacology · 2021Review
- Oral Dimethyl Fumarate Reduces Peripheral Neuropathic Pain in Rodents via NFE2L2 Antioxidant Signaling.Anesthesiology · 2020Article
- Opioid antagonists as potential therapeutics for ischemic stroke.Progress in neurobiology · 2019Review
- Taurine protects noradrenergic locus coeruleus neurons in a mouse Parkinson's disease model by inhibiting microglial M1 polarization.Amino acids · 2018Article
- 17Oxidative medicine and cellular longevity · 2018Article
- Autonomous CaMKII Activity as a Drug Target for Histological and Functional Neuroprotection after Resuscitation from Cardiac Arrest.Cell reports · 2017Article
- Naltrexone Inhibits IL-6 and TNFα Production in Human Immune Cell Subsets following Stimulation with Ligands for Intracellular Toll-Like Receptors.Frontiers in immunology · 2017Article
- EEG power as a biomarker to predict the outcome after cardiac arrest and cardiopulmonary resuscitation induced global ischemia.Life sciences · 2016Article
- Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Despite dramatic improvement in cardiopulmonary resuscitation (CPR) and other techniques for cardiac arrest (CA), the majority of survivors continue to show signs of decreased memory or executive cognitive function. Such memory impairment may be due to hippocampal CA1 neuronal death, which is delayed by several days after CA/CPR. Classical microgliosis in the CA1 region may contribute to neuronal death, yet the role of a key activation receptor Toll Like Receptor 4 (TLR4) has not been previously investigated for such neuronal death after CA/CPR. We show that (+)-naltrexone was neuroprotective after CA/CPR. TLR4 blockade was associated with decreased expression of markers for microglial/macrophage activation and T cell and B cell infiltration, as well as decreased pro-inflammatory cytokine levels. Notably, IL-10 expression was elevated in response to CA/CPR, but was not attenuated by (+)-naltrexone, suggesting that the local monocyte/microglial phenotype had shifted towards alternative activation. This was confirmed by elevated expression of Arginase-1, and decreased expression of NFκB p65 subunit. Thus, (+)-naltrexone and other TLR4 antagonists may represent a novel therapeutic strategy to alleviate the substantial burden of memory or executive cognitive function impairment after CA/CPR.
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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.