ArticleNeurobiology of disease2014
Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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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
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Marine-derived n-3 fatty acids therapy for stroke.The Cochrane database of systematic reviews · 2022Pooled it
- Marine-derived n-3 fatty acids therapy for stroke.The Cochrane database of systematic reviews · 2019Pooled it
- Untargeted Metabolomic Signature of Mice with Ischemic Stroke.Metabolites · 2026Article
- 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
- Metabolic Symbiosis Between Cancer Cells and Endothelial Cells: A Key Driver of Tumor Angiogenesis.Advances in experimental medicine and biology · 2026Review
- Genetic deletion of microRNA-15a/16-1 in pericytes stimulates cerebral angiogenesis and promotes functional recovery after ischemic stroke.Angiogenesis · 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
- Treg Upregulation by Treadmill Training Accelerates Myelin Repair Post-Ischemia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Fish-derived biomaterials for tissue engineering: advances in scaffold fabrication and applications in regenerative medicine and cancer therapy.Theranostics · 2025Review
- Maternal n-3 enriched diet reprograms the offspring neurovascular transcriptome and blunts inflammation induced by endotoxin in the neonate.Journal of neuroinflammation · 2024Article
- Astrocytes in functional recovery following central nervous system injuries.The Journal of physiology · 2024Review
- Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke.Biomarker research · 2024Review
- Molecular Pathogenesis of Ischemic and Hemorrhagic Strokes: Background and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Metabolic Reprogramming in Gliocyte Post-cerebral Ischemia/ Reperfusion: From Pathophysiology to Therapeutic Potential.Current neuropharmacology · 2024Review
- Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathwayPharmaceutical biology · 2023Article
- Gut Dysbiosis: A New Avenue for Stroke Prevention and Therapeutics.Biomedicines · 2023Article
- Vagus nerve stimulation is a potential treatment for ischemic stroke.Neural regeneration research · 2023Article
- Midlife omega-3 fatty acid intake predicts later life white matter microstructure in an age- and APOE-dependent manner.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Impact of Nutritional Status on Outcomes of Stroke Survivors: A Post Hoc Analysis of the NHANES.Nutrients · 2023Article
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Stroke is a devastating neurological disorder and one of the leading causes of death and serious disability. After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke. In the present study, we tested the hypothesis that post-stroke angiogenesis would be enhanced by omega-3 polyunsaturated fatty acids (n-3 PUFAs), a major component of dietary fish oil. To this end, we found that transgenic fat-1 mice that overproduce n-3 PUFAs exhibited long-term behavioral and histological protection against transient focal cerebral ischemia (tFCI). Importantly, fat-1 transgenic mice also exhibited robust improvements in revascularization and angiogenesis compared to wild type littermates, suggesting a potential role for n-3 fatty acids in post-stroke cerebrovascular remodeling. Mechanistically, n-3 PUFAs induced upregulation of angiopoietin 2 (Ang 2) in astrocytes after tFCI and stimulated extracellular Ang 2 release from cultured astrocytes after oxygen and glucose deprivation. Ang 2 facilitated endothelial proliferation and barrier formation in vitro by potentiating the effects of VEGF on phospholipase Cγ1 and Src signaling. Consistent with these findings, blockade of Src activity in post-stroke fat-1 mice impaired n-3 PUFA-induced angiogenesis and exacerbated long-term neurological outcomes. Taken together, our findings strongly suggest that n-3 PUFA supplementation is a potential angiogenic treatment capable of augmenting brain repair and improving long-term functional recovery after cerebral ischemia.
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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.