{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:52:29Z","timestamp":1789192349812,"version":"build-2803163510"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>\n              Omega-3 polyunsaturated fatty acids (\n              <jats:italic>n-3<\/jats:italic>\n              PUFAs) attenuate neonatal hypoxic\/ischemic (H\/I) brain damage, but the underlying mechanisms are not fully understood. This study tested the hypothesis that\n              <jats:italic>n-3<\/jats:italic>\n              PUFAs enhance Akt-dependent prosurvival signaling by promoting the biosynthesis of phosphatidylserine in neuronal cell membranes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              Dietary\n              <jats:italic>n-3<\/jats:italic>\n              PUFA supplementation was initiated on the second day of pregnancy in dams. H\/I was induced in 7-day-old rat pups by ipsilateral common carotid artery occlusion followed by hypoxia (8% oxygen for 2.5 hours). Neurological outcomes, brain tissue loss, cell death, and the activation of signaling events were assessed after H\/I. The effects of\n              <jats:italic>n-3<\/jats:italic>\n              PUFAs (docosahexaenoic acid and eicosapentaenoic acid) on oxygen-glucose deprivation\u2013induced cell death and the underlying mechanism of protection were also examined in primary cortical neuron cultures.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              <jats:italic>n-3<\/jats:italic>\n              PUFAs reduced brain tissue loss at 7 days after H\/I and improved neurological outcomes, whereas inhibition of PI3K\/Akt signaling by LY294002 partially abrogated this neuroprotective effect. Docosahexaenoic acid\/eicosapentaenoic acid also prevented ischemic neuronal death through the Akt prosurvival pathway in vitro. Furthermore, docosahexaenoic acid\/eicosapentaenoic acid increased the production of phosphatidylserine, the major membrane-bound phospholipids, after ischemia both in vitro and in vivo. A reduction in membrane phosphatidylserine by shRNA-mediated knockdown of phosphatidylserine synthetase-1 attenuated Akt activation and neuronal survival after docosahexaenoic acid\/eicosapentaenoic acid treatment in the oxygen-glucose deprivation model.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              <jats:italic>n-3<\/jats:italic>\n              PUFAs robustly protect against H\/I-induced brain damage in neonates by activating Akt prosurvival pathway in compromised neurons. In addition,\n              <jats:italic>n-3<\/jats:italic>\n              PUFAs promote the formation of membrane phosphatidylserine, thereby promoting Akt activity and improving cellular survival.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.115.010815","type":"journal-article","created":{"date-parts":[[2015,9,16]],"date-time":"2015-09-16T02:09:42Z","timestamp":1442369382000},"page":"2943-2950","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["<i>n<\/i>\n            -3 Polyunsaturated Fatty Acids Reduce Neonatal Hypoxic\/Ischemic Brain Injury by Promoting Phosphatidylserine Formation and Akt Signaling"],"prefix":"10.1161","volume":"46","author":[{"given":"Wenting","family":"Zhang","sequence":"first","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (W.Z., J.L., X.H., P.L., Y.G., J.C.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); Geriatric Research, Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (W.Z., J.L., X.H., P.L., Y.G., J.C.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); Geriatric Research, Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Hu","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (W.Z., J.L., X.H., P.L., Y.G., J.C.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); Geriatric Research, Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Li","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (W.Z., J.L., X.H., P.L., Y.G., J.C.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); Geriatric Research, Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehana K.","family":"Leak","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (W.Z., J.L., X.H., P.L., Y.G., J.C.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); Geriatric Research, Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Gao","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (W.Z., J.L., X.H., P.L., Y.G., J.C.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); Geriatric Research, Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"From the State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (W.Z., J.L., X.H., P.L., Y.G., J.C.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (X.H., J.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); Geriatric Research, Educational and Clinical Center, Veterans Affairs..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.06.094"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200112000-00009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000258102.18836.ca"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4829fje"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.3.304"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.24.3130"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-001-0798-1"},{"key":"e_1_3_3_9_2","first-page":"207","article-title":"Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.","volume":"12","author":"Kidd PM","year":"2007","unstructured":"Kidd PM. 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