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Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction
Luo, Chuanming1,2; Ren, Huixia1; Yao, Xiaoli3; Shi, Zhe1; Liang, Fengyin3; Kang, Jing X.4; Wan, Jian-bo1; Pei, Zhong3; Su, Kuan-Pin5; Su, Huanxing1
Source PublicationEBIOMEDICINE

Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these microvascular ischemic lesions. In the present study, the "single cortical microinfarct model" generated via occluding a penetrating arteriole by femtosecond laser ablation and the "multiple diffuse microinfarcts model" induced by unilateral injection of cholesterol crystals through the internal carotid artery were established to investigate the pathophysiological mechanisms underlying the evolution of microinfarcts and the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on alleviating microinfarct burdens and functional deficits. The occlusion of a single penetrating arteriole led to a distinct cortical microinfarct, which manifested as neuronal loss and occupation of activated glial cells in the ischemic core. Using Fat-1 transgenic mice and fish oil supplements, we demonstrated that both endogenously-generated and exogenously-delivered omega-3 PUFAs significantly inhibited the activation of receptor-interacting serine/threonine protein kinases 1 (RIPK1) and its downstream apoptosis-associated proteins, mitigated cell apoptosis, and anatomically reduced the microinfarct size. The protective effects of omega-3 PUFAs against microinfarcts were further verified in a multiple diffuse microinfarcts model, where omega-3 PUFAs significantly attenuated cell apoptosis as revealed by TUNEL staining, alleviated the diffuse microinfarct burdens and remarkably improved the functional deficits as evidenced by reduced spontaneous anxiety, increased preference for the novel object, and improved hippocampal-based learning and short-term memory. Together, these findings demonstrate that enriched brain omega-3 PUFAs are effective for reducing microinfarct burdens and improving the function deficits, which support the clinical research and application of omega-3 PUFAs in the treatment or prophylaxis in vascular dementia. (C) 2018 The Authors. Published by Elsevier B.V.

KeywordFish Oil Cognitive Decline Vascular Dementia Neuropsychiatric Disorders
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Indexed BySCI
WOS Research AreaGeneral & Internal Medicine ; Research & Experimental Medicine
WOS SubjectMedicine, General & Internal ; Medicine, Research & Experimental
WOS IDWOS:000436312000010
The Source to ArticleWOS
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Cited Times [WOS]:9   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorSu, Huanxing
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Department of Neurology, Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 510080, China
3.Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, China
4.Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
5.Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, College of Medicine, China Medical University, Taichung, Taiwan
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Luo, Chuanming,Ren, Huixia,Yao, Xiaoli,et al. Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction[J]. EBIOMEDICINE,2018,32:50-61.
APA Luo, Chuanming.,Ren, Huixia.,Yao, Xiaoli.,Shi, Zhe.,Liang, Fengyin.,...&Su, Huanxing.(2018).Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction.EBIOMEDICINE,32,50-61.
MLA Luo, Chuanming,et al."Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction".EBIOMEDICINE 32(2018):50-61.
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