PMID- 31898186 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20220928 IS - 1868-601X (Electronic) IS - 1868-4483 (Linking) VI - 11 IP - 5 DP - 2020 Oct TI - Human Milk Oligosaccharide 2'-Fucosyllactose Reduces Neurodegeneration in Stroke Brain. PG - 1001-1011 LID - 10.1007/s12975-019-00774-z [doi] AB - 2'-Fucosyllactose (2'-FL) is a major oligosaccharide in human milk and is present at trace levels in cow milk. 2'-FL reduces inflammation in the gastrointestinal tract. Its action in the central nervous system has not been well characterized. The purpose of this study is to determine 2'-FL-mediated neural protection and repair in culture and stroke brain. In rat primary cortical neuronal cultures, 2'-FL significantly antagonized N-methyl-D-aspartate (NMDA) or glutamate-mediated changes in ATP production, MAP2 immunoreactivity, and TUNEL. The influx of Ca(++) (Ca(++)i) was examined in primary cortical neurons expressing GCaMP5, an endogenous calcium probe. NMDA increased Ca(++)i; 2'-FL significantly attenuated this reaction. In a rat middle cerebral artery occlusion model of stroke, we found that intracerebroventricular pretreatment or oral posttreatment with 2'-FL significantly reduced brain infarction, mitigated microglial activation, improved locomotor activity, and upregulated brain-derived neurotrophic factor (BDNF) expression. Post-stroke delivery of 2'-FL increased bromodeoxyuridine (BrdU) labeling in the perilesioned area. These BrdU cells co-expressed NeuN, or nestin, or GFAP. Using subventricular Matrigel cultures, we demonstrated that 2'-FL increased cell migration from subventricular zone explant. This response was reduced by anti-BDNF blocking antibody. In conclusion, our data suggest that 2'-FL has neuroprotective action through inhibition of Ca(++)i, inflammation, and apoptosis. Posttreatment with 2'-FL facilitates neural repair in stroke brain. FAU - Wu, Kou-Jen AU - Wu KJ AD - Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli, Taiwan. FAU - Chen, Yun-Hsiang AU - Chen YH AD - Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan. FAU - Bae, Eun-Kyung AU - Bae EK AD - Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli, Taiwan. FAU - Song, YoungHa AU - Song Y AD - Advanced Protein Technologies Corporation, Gyeonggi-Do, South Korea. FAU - Min, WonKi AU - Min W AD - Department of Food Science and Development, Kyungil University, Gyeongsan, South Korea. FAU - Yu, Seong-Jin AU - Yu SJ AUID- ORCID: 0000-0001-7500-5883 AD - Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli, Taiwan. b7508@nhri.org.tw. LA - eng GR - 106-2320-B-400 -029 -MY2/Ministry of Science and Technology, Taiwan/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200102 PL - United States TA - Transl Stroke Res JT - Translational stroke research JID - 101517297 RN - 0 (Oligosaccharides) RN - 0 (Trisaccharides) RN - XO2533XO8R (2'-fucosyllactose) SB - IM MH - Animals MH - Brain/*drug effects/metabolism MH - Cell Movement/drug effects MH - Cells, Cultured MH - Disease Models, Animal MH - Female MH - Humans MH - Male MH - Milk, Human/*metabolism MH - Neurons/*drug effects/metabolism MH - Oligosaccharides/metabolism/*pharmacology MH - Rats, Sprague-Dawley MH - Trisaccharides/*pharmacology OTO - NOTNLM OT - 2'-Fucosyllactose OT - Human milk OT - Inflammation OT - Neuroprotection OT - Stroke EDAT- 2020/01/04 06:00 MHDA- 2021/07/20 06:00 CRDT- 2020/01/04 06:00 PHST- 2019/09/15 00:00 [received] PHST- 2019/12/17 00:00 [accepted] PHST- 2019/12/12 00:00 [revised] PHST- 2020/01/04 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] PHST- 2020/01/04 06:00 [entrez] AID - 10.1007/s12975-019-00774-z [pii] AID - 10.1007/s12975-019-00774-z [doi] PST - ppublish SO - Transl Stroke Res. 2020 Oct;11(5):1001-1011. doi: 10.1007/s12975-019-00774-z. Epub 2020 Jan 2.