Omega-3 polyunsaturated fatty acids mitigate blood–brain barrier disruption after hypoxic–ischemic brain injury

Wenting Zhang; Hui Zhang; Hongfeng Mu; Wen Zhu; Xiaoyan Jiang; Xiaoming Hu; Yejie Shi; Rehana K. Leak; Qiang Dong; Jun Chen; Yanqin Gao

Neurobiology of Disease (Jul 2016)

Omega-3 polyunsaturated fatty acids mitigate blood–brain barrier disruption after hypoxic–ischemic brain injury

Wenting Zhang,
Hui Zhang,
Hongfeng Mu,
Wen Zhu,
Xiaoyan Jiang,
Xiaoming Hu,
Yejie Shi,
Rehana K. Leak,
Qiang Dong,
Jun Chen,
Yanqin Gao

Affiliations

Wenting Zhang: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Hui Zhang: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Department of Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China
Hongfeng Mu: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Wen Zhu: Center of Cerebrovascular Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Xiaoyan Jiang: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Xiaoming Hu: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Yejie Shi: Center of Cerebrovascular Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Rehana K. Leak: Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA
Qiang Dong: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Department of Neurology of Huashan Hospital, Fudan University, Shanghai 200032, China
Jun Chen: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, 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; Correspondence to: J. Chen, Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, S507 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh, PA 15213, USA.
Yanqin Gao: State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Center of Cerebrovascular Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Correspondence to: Y. Gao, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.

Journal volume & issue: Vol. 91
pp. 37 – 46

Abstract

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Omega-3 polyunsaturated fatty acids (n‐3 PUFAs) have been shown to protect the neonatal brain against hypoxic/ischemic (H/I) injury. However, the mechanism of n‐3 PUFA-afforded neuroprotection is not well understood. One major determinant of H/I vulnerability is the permeability of the blood–brain barrier (BBB). Therefore, we examined the effects of n‐3 PUFAs on BBB integrity after neonatal H/I. Female rats were fed a diet with or without n‐3 PUFA enrichment from day 2 of pregnancy to 14 days after parturition. H/I was introduced in 7 day-old offspring. We observed relatively rapid BBB penetration of the small molecule cadaverine (640 Da) at 4 h post-H/I and a delayed penetration of larger dextrans (3 kD–40 kD) 24–48 h after injury. Surprisingly, the neonatal BBB was impermeable to Evans Blue or 70 kD dextran leakage for up to 48 h post-H/I, despite evidence of IgG extravasation at this time. As expected, n‐3 PUFAs ameliorated H/I-induced BBB damage, as shown by reductions in tracer efflux and IgG extravasation, preservation of BBB ultrastructure, and enhanced tight junction protein expression. Furthermore, n‐3 PUFAs prevented the elevation in matrix metalloproteinase (MMP) activity in the brain and blood after H/I. Thus, n‐3 PUFAs may protect neonates against BBB damage by blunting MMPs activation after H/I.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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