title: Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke.
abstract: Stroke is a devastating neurological disease with no satisfactory therapies to preserve long-term neurological function, perhaps due to the sole emphasis on neuronal survival in most preclinical studies. Recent studies have revealed the importance of protecting multiple cell types in the injured brain, such as oligodendrocytes and components of the neurovascular unit, before long-lasting recovery of function can be achieved. For example, revascularization in the ischemic penumbra is critical to provide various neurotrophic factors that enhance the survival and activity of neurons and other progenitor cells, such as oligodendrocyte precursor cells. In the present study, we hypothesized that chronic dietary supplementation with fish oil promotes post-stroke angiogenesis, neurogenesis, and oligodendrogenesis, thereby leading to long-term functional improvements. Mice received dietary supplementation with n-3 PUFA-enriched fish oil for three months before and up to one month after stroke. As expected, dietary n-3 PUFAs significantly increased levels of n-3 PUFAs in the brain and improved long-term behavioral outcomes after cerebral ischemia. n-3 PUFAs also robustly improved revascularization and angiogenesis and boosted the survival of NeuN/BrdU labeled newborn neurons up to 35days after stroke injury. Furthermore, these pro-neurogenic effects were accompanied by robust oligodendrogenesis. Thus, this is the first study to demonstrate that chronic dietary intake of n-3 PUFAs is an effective prophylactic measure not only to protect against ischemic injury for the long term but also to actively promote neurovascular restorative dynamics and brain repair.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, and Departments of Anesthesiology and Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address: wtzhang@fudan.edu.cn.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, and Departments of Anesthesiology and Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Hailian
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, and Departments of Anesthesiology and Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA.
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors.forename: Yejie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, and Departments of Anesthesiology and Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, and Departments of Anesthesiology and Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, and Departments of Anesthesiology and Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA. Electronic address: chenj2@upmc.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002560:Cerebrovascular Circulation / Q000502:physiology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009422:Nervous System Diseases / Q000178:diet therapy* / Q000209:etiology*; D055495:Neurogenesis / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D013997:Time Factors
chemical_list: D000089622:Doublecortin Domain Proteins; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine
keywords: Angiogenesis; Angiopoietin 1; Docosahexaenoic acid; Eicosapentaenoic acid; Neurogenesis; Oligodendrocyte precursor cell; Oligodendrogenesis; Revascularization