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N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice
We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/...
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| Published in: | PloS one 2013-02, Vol.8 (2), p.e56233-e56233 |
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| creator | Williams, Jill J Mayurasakorn, Korapat Vannucci, Susan J Mastropietro, Christopher Bazan, Nicolas G Ten, Vadim S Deckelbaum, Richard J |
| description | We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O(2) for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1-0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p |
| doi_str_mv | 10.1371/journal.pone.0056233 |
| format | article |
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We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O(2) for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1-0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0056233</identifier><identifier>PMID: 23437099</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Animals, Newborn ; Apoptosis ; Biology ; Bleeding Time ; Blood flow ; Blood Glucose - metabolism ; Brain ; Brain - blood supply ; Brain - drug effects ; Brain - pathology ; Brain - physiopathology ; Brain Infarction - drug therapy ; Brain Infarction - pathology ; Brain Infarction - physiopathology ; Brain injuries ; Brain injury ; Cardiovascular disease ; Carotid artery ; Cerebral blood flow ; Cerebral infarction ; Cerebrovascular Circulation - drug effects ; Docosahexaenoic acid ; Docosahexaenoic Acids - administration & dosage ; Docosahexaenoic Acids - pharmacology ; Docosahexaenoic Acids - therapeutic use ; Eicosapentaenoic acid ; Eicosapentaenoic Acid - administration & dosage ; Eicosapentaenoic Acid - pharmacology ; Eicosapentaenoic Acid - therapeutic use ; Emulsions ; Fatty acids ; Fatty Acids, Omega-3 - administration & dosage ; Fatty Acids, Omega-3 - pharmacology ; Fatty Acids, Omega-3 - therapeutic use ; Fatty Acids, Omega-6 - administration & dosage ; Fatty Acids, Omega-6 - pharmacology ; Fatty Acids, Omega-6 - therapeutic use ; Fish oils ; Gene expression ; Head injuries ; Health aspects ; House mouse ; Hypoxia ; Hypoxia-Ischemia, Brain - drug therapy ; Hypoxia-Ischemia, Brain - pathology ; Hypoxia-Ischemia, Brain - physiopathology ; Infarction ; Injection ; Injections, Intraperitoneal ; Ischemia ; Laboratory animals ; Lipids ; Medicin och hälsovetenskap ; Medicine ; Metabolism ; Mice ; Mice, Inbred C57BL ; Neonates ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Newborn babies ; Newborn infants ; Nutrition ; Omega 3 fatty acids ; Oxidative stress ; Pediatrics ; Rodents ; Spinal cord injuries ; Stroke ; Surgeons ; Time Factors ; Traumatic brain injury ; Triglycerides ; Triglycerides - blood ; Triglycerides - pharmacology ; Triglycerides - therapeutic use ; Unsaturated fatty acids</subject><ispartof>PloS one, 2013-02, Vol.8 (2), p.e56233-e56233</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Williams et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Williams et al 2013 Williams et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c742t-e7a86c912d58a006bd1316c1b51a1fc2e104ac318b57259c787f84d47c14eff93</citedby><cites>FETCH-LOGICAL-c742t-e7a86c912d58a006bd1316c1b51a1fc2e104ac318b57259c787f84d47c14eff93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1330881967/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1330881967?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23437099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:126344334$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Borlongan, Cesar V.</contributor><creatorcontrib>Williams, Jill J</creatorcontrib><creatorcontrib>Mayurasakorn, Korapat</creatorcontrib><creatorcontrib>Vannucci, Susan J</creatorcontrib><creatorcontrib>Mastropietro, Christopher</creatorcontrib><creatorcontrib>Bazan, Nicolas G</creatorcontrib><creatorcontrib>Ten, Vadim S</creatorcontrib><creatorcontrib>Deckelbaum, Richard J</creatorcontrib><title>N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O(2) for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1-0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Bleeding Time</subject><subject>Blood flow</subject><subject>Blood Glucose - metabolism</subject><subject>Brain</subject><subject>Brain - blood supply</subject><subject>Brain - drug effects</subject><subject>Brain - pathology</subject><subject>Brain - physiopathology</subject><subject>Brain Infarction - drug therapy</subject><subject>Brain Infarction - pathology</subject><subject>Brain Infarction - physiopathology</subject><subject>Brain injuries</subject><subject>Brain injury</subject><subject>Cardiovascular disease</subject><subject>Carotid artery</subject><subject>Cerebral blood flow</subject><subject>Cerebral infarction</subject><subject>Cerebrovascular Circulation - drug effects</subject><subject>Docosahexaenoic acid</subject><subject>Docosahexaenoic Acids - administration & dosage</subject><subject>Docosahexaenoic Acids - pharmacology</subject><subject>Docosahexaenoic Acids - therapeutic use</subject><subject>Eicosapentaenoic acid</subject><subject>Eicosapentaenoic Acid - administration & dosage</subject><subject>Eicosapentaenoic Acid - pharmacology</subject><subject>Eicosapentaenoic Acid - therapeutic use</subject><subject>Emulsions</subject><subject>Fatty acids</subject><subject>Fatty Acids, Omega-3 - administration & dosage</subject><subject>Fatty Acids, Omega-3 - pharmacology</subject><subject>Fatty Acids, Omega-3 - therapeutic use</subject><subject>Fatty Acids, Omega-6 - administration & dosage</subject><subject>Fatty Acids, Omega-6 - pharmacology</subject><subject>Fatty Acids, Omega-6 - therapeutic use</subject><subject>Fish oils</subject><subject>Gene expression</subject><subject>Head injuries</subject><subject>Health aspects</subject><subject>House mouse</subject><subject>Hypoxia</subject><subject>Hypoxia-Ischemia, Brain - drug therapy</subject><subject>Hypoxia-Ischemia, Brain - pathology</subject><subject>Hypoxia-Ischemia, Brain - physiopathology</subject><subject>Infarction</subject><subject>Injection</subject><subject>Injections, Intraperitoneal</subject><subject>Ischemia</subject><subject>Laboratory animals</subject><subject>Lipids</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neonates</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Newborn babies</subject><subject>Newborn infants</subject><subject>Nutrition</subject><subject>Omega 3 fatty acids</subject><subject>Oxidative stress</subject><subject>Pediatrics</subject><subject>Rodents</subject><subject>Spinal cord injuries</subject><subject>Stroke</subject><subject>Surgeons</subject><subject>Time Factors</subject><subject>Traumatic brain injury</subject><subject>Triglycerides</subject><subject>Triglycerides - blood</subject><subject>Triglycerides - pharmacology</subject><subject>Triglycerides - therapeutic use</subject><subject>Unsaturated fatty acids</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7jr6D0QLgujFjE3SNumNsCx-DCwu-HUb0vR0mrHTdJN03fn3njrdZSp7ISUknD7nTfKenCh6TpIVYZy829rBdapd9baDVZJkOWXsQXRKCkaXOU3Yw6P1SfTE-y1CTOT54-iEspTxpChOo-svSxbXKoR9rLSpYmd0EwdnNu1egzMVxLAbWm9s52PlIO5gcLZ3NoAO5hpiVQdwMaJQOtXGzb63N0YvjdcN7IyOTbcd3B4nzLSdCshgGJ5Gj2rVeng2zYvox8cP388_Ly8uP63Pzy6Wmqc0LIErkeuC0CoTKknysiKM5JqUGVGk1hRIkirNiCgzTrNCc8FrkVYp1ySFui7YInp50O1b6-VkmZeEsUQIUuQcifWBqKzayt6ZnXJ7aZWRfwPWbaRywegWZMHrMgdWEMHSlLJK4aB4kpzoqmIZRa3ioOV_Qz-UMzX0rJJT_JcZh_QgCc1Ri2E5FtH76aRDuYNKQxfQ0LnE7E9nGrmx15JlnAus7CJ6Mwk4ezWAD3KHVYC2Vej8MN4ZN8s4ESP66h_0fmcmaqPw8qarLe6rR1F5lnKBz6rIBFKreyj8qrH--DZrg_FZwttZAjIBbsJGDd7L9bev_89e_pyzr4_YBlQbGm_bIYxvdw6mB1A7672D-s5kksixtW7dkGNryam1MO3FcYHukm57if0BVvEgCQ</recordid><startdate>20130220</startdate><enddate>20130220</enddate><creator>Williams, Jill J</creator><creator>Mayurasakorn, Korapat</creator><creator>Vannucci, Susan J</creator><creator>Mastropietro, Christopher</creator><creator>Bazan, Nicolas G</creator><creator>Ten, Vadim S</creator><creator>Deckelbaum, Richard J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20130220</creationdate><title>N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice</title><author>Williams, Jill J ; Mayurasakorn, Korapat ; Vannucci, Susan J ; Mastropietro, Christopher ; Bazan, Nicolas G ; Ten, Vadim S ; Deckelbaum, Richard J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c742t-e7a86c912d58a006bd1316c1b51a1fc2e104ac318b57259c787f84d47c14eff93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Bleeding Time</topic><topic>Blood flow</topic><topic>Blood Glucose - metabolism</topic><topic>Brain</topic><topic>Brain - blood supply</topic><topic>Brain - drug effects</topic><topic>Brain - pathology</topic><topic>Brain - physiopathology</topic><topic>Brain Infarction - drug therapy</topic><topic>Brain Infarction - pathology</topic><topic>Brain Infarction - physiopathology</topic><topic>Brain injuries</topic><topic>Brain injury</topic><topic>Cardiovascular disease</topic><topic>Carotid artery</topic><topic>Cerebral blood flow</topic><topic>Cerebral infarction</topic><topic>Cerebrovascular Circulation - drug effects</topic><topic>Docosahexaenoic acid</topic><topic>Docosahexaenoic Acids - administration & dosage</topic><topic>Docosahexaenoic Acids - pharmacology</topic><topic>Docosahexaenoic Acids - therapeutic use</topic><topic>Eicosapentaenoic acid</topic><topic>Eicosapentaenoic Acid - administration & dosage</topic><topic>Eicosapentaenoic Acid - pharmacology</topic><topic>Eicosapentaenoic Acid - therapeutic use</topic><topic>Emulsions</topic><topic>Fatty acids</topic><topic>Fatty Acids, Omega-3 - administration & dosage</topic><topic>Fatty Acids, Omega-3 - pharmacology</topic><topic>Fatty Acids, Omega-3 - therapeutic use</topic><topic>Fatty Acids, Omega-6 - administration & dosage</topic><topic>Fatty Acids, Omega-6 - pharmacology</topic><topic>Fatty Acids, Omega-6 - therapeutic use</topic><topic>Fish oils</topic><topic>Gene expression</topic><topic>Head injuries</topic><topic>Health aspects</topic><topic>House mouse</topic><topic>Hypoxia</topic><topic>Hypoxia-Ischemia, Brain - drug therapy</topic><topic>Hypoxia-Ischemia, Brain - pathology</topic><topic>Hypoxia-Ischemia, Brain - physiopathology</topic><topic>Infarction</topic><topic>Injection</topic><topic>Injections, Intraperitoneal</topic><topic>Ischemia</topic><topic>Laboratory animals</topic><topic>Lipids</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neonates</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Newborn babies</topic><topic>Newborn infants</topic><topic>Nutrition</topic><topic>Omega 3 fatty acids</topic><topic>Oxidative stress</topic><topic>Pediatrics</topic><topic>Rodents</topic><topic>Spinal cord injuries</topic><topic>Stroke</topic><topic>Surgeons</topic><topic>Time Factors</topic><topic>Traumatic brain injury</topic><topic>Triglycerides</topic><topic>Triglycerides - blood</topic><topic>Triglycerides - pharmacology</topic><topic>Triglycerides - therapeutic use</topic><topic>Unsaturated fatty acids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Williams, Jill J</creatorcontrib><creatorcontrib>Mayurasakorn, Korapat</creatorcontrib><creatorcontrib>Vannucci, Susan J</creatorcontrib><creatorcontrib>Mastropietro, Christopher</creatorcontrib><creatorcontrib>Bazan, Nicolas G</creatorcontrib><creatorcontrib>Ten, Vadim S</creatorcontrib><creatorcontrib>Deckelbaum, Richard J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale_Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Williams, Jill J</au><au>Mayurasakorn, Korapat</au><au>Vannucci, Susan J</au><au>Mastropietro, Christopher</au><au>Bazan, Nicolas G</au><au>Ten, Vadim S</au><au>Deckelbaum, Richard J</au><au>Borlongan, Cesar V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-02-20</date><risdate>2013</risdate><volume>8</volume><issue>2</issue><spage>e56233</spage><epage>e56233</epage><pages>e56233-e56233</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O(2) for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1-0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23437099</pmid><doi>10.1371/journal.pone.0056233</doi><tpages>e56233</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-02, Vol.8 (2), p.e56233-e56233 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1330881967 |
| source | PubMed Central Free; Publicly Available Content Database |
| subjects | Animals Animals, Newborn Apoptosis Biology Bleeding Time Blood flow Blood Glucose - metabolism Brain Brain - blood supply Brain - drug effects Brain - pathology Brain - physiopathology Brain Infarction - drug therapy Brain Infarction - pathology Brain Infarction - physiopathology Brain injuries Brain injury Cardiovascular disease Carotid artery Cerebral blood flow Cerebral infarction Cerebrovascular Circulation - drug effects Docosahexaenoic acid Docosahexaenoic Acids - administration & dosage Docosahexaenoic Acids - pharmacology Docosahexaenoic Acids - therapeutic use Eicosapentaenoic acid Eicosapentaenoic Acid - administration & dosage Eicosapentaenoic Acid - pharmacology Eicosapentaenoic Acid - therapeutic use Emulsions Fatty acids Fatty Acids, Omega-3 - administration & dosage Fatty Acids, Omega-3 - pharmacology Fatty Acids, Omega-3 - therapeutic use Fatty Acids, Omega-6 - administration & dosage Fatty Acids, Omega-6 - pharmacology Fatty Acids, Omega-6 - therapeutic use Fish oils Gene expression Head injuries Health aspects House mouse Hypoxia Hypoxia-Ischemia, Brain - drug therapy Hypoxia-Ischemia, Brain - pathology Hypoxia-Ischemia, Brain - physiopathology Infarction Injection Injections, Intraperitoneal Ischemia Laboratory animals Lipids Medicin och hälsovetenskap Medicine Metabolism Mice Mice, Inbred C57BL Neonates Neuroprotection Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Newborn babies Newborn infants Nutrition Omega 3 fatty acids Oxidative stress Pediatrics Rodents Spinal cord injuries Stroke Surgeons Time Factors Traumatic brain injury Triglycerides Triglycerides - blood Triglycerides - pharmacology Triglycerides - therapeutic use Unsaturated fatty acids |
| title | N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice |
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