ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
104 citing papers in PubMed, 4 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19.Brain, behavior, and immunity · 2022Pooled it
- Marine-derived n-3 fatty acids therapy for stroke.The Cochrane database of systematic reviews · 2022Pooled it
- Omega-3 Polyunsaturated Fatty Acids and Stroke Burden.International journal of molecular sciences · 2019Pooled it
- Marine-derived n-3 fatty acids therapy for stroke.The Cochrane database of systematic reviews · 2019Pooled it
- Omega-3 Fatty Acids and Alzheimer's Disease: Toward a New Understanding of Neuroprotective Mechanisms and Intervention Strategies.Marine drugs · 2026Review
- Dietary Lipids and Lipid-Mediated Signaling Neurovascular Unit Dysfunction: Implications for Alzheimer's and Parkinson's Diseases Pathogenesis.Molecular neurobiology · 2026Review
- Anti-Inflammatory and Antioxidant Effects of ω-3 Polyunsaturated Fatty Acids on Astrocytes and Their Implications for the Blood-Brain Barrier's Integrity and Function.International journal of molecular sciences · 2026Review
- Lipid Messengers: Mechanisms and Clinical Applications of Exosomal Lipids in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, Pharmacological, Nanoparticle, and Gene Therapy Approaches.CNS & neurological disorders drug targets · 2026Review
- Protective Effects of Fish Oil Against Brain Impairment in Rats with Chronic Ethanol-Induced Liver Damage Involving the NRF2 Pathway and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Bioactivity and Neuroprotective Effects of Extra Virgin Olive Oil in a Mouse Model of Cerebral Ischemia: An In Vitro and In Vivo Study.International journal of molecular sciences · 2025Article
- Aging-associated Aberrant Mitochondrial Redox Signaling, Physical Activity, and Sarcopenia.Current aging science · 2025Review
- Insights of early feeding regime supplemented with glutamine and various levels of omega-3 in broiler chickens: growth performance, muscle building, antioxidant capacity, intestinal barriers health and defense against mixedThe veterinary quarterly · 2024Article
- Capsaicin Modulates Hepatic and Intestinal Inflammation and Oxidative Stress by Regulating the Colon Microbiota.Antioxidants (Basel, Switzerland) · 2024Article
- Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke.Biomarker research · 2024Review
- Ischemic Brain Injury: Involvement of Lipids in the Pathophysiology of Stroke and Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2024Review
- Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows.Journal of animal science and biotechnology · 2024Article
- The cell-specific roles of Nrf2 in acute and chronic phases of ischemic stroke.CNS neuroscience & therapeutics · 2024Review
- Age-Dependent Changes in Nrf2/Keap1 and Target Antioxidant Protein Expression Correlate to Lipoxidative Adducts, and Are Modulated by Dietary N-3 LCPUFA in the Hippocampus of Mice.Antioxidants (Basel, Switzerland) · 2024Article
- The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics.International journal of medical sciences · 2024Review
44 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
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.
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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.