Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep
Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestat...
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| Veröffentlicht in: | Journal of cerebral blood flow and metabolism 2017-03, Vol.37 (3), p.1080-1094 |
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| container_title | Journal of cerebral blood flow and metabolism |
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| creator | Wassink, Guido Davidson, Joanne O Dhillon, Simerdeep K Fraser, Mhoyra Galinsky, Robert Bennet, Laura Gunn, Alistair J |
| description | Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832.5 IU/h), starting 30 min after asphyxia and continued until 72 h. Recombinant human erythropoietin reduced neuronal loss and numbers of caspase-3-positive cells in the striatal caudate nucleus, CA3 and dentate gyrus of the hippocampus, and thalamic medial nucleus (P |
| doi_str_mv | 10.1177/0271678X16650455 |
| format | Article |
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Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832.5 IU/h), starting 30 min after asphyxia and continued until 72 h. Recombinant human erythropoietin reduced neuronal loss and numbers of caspase-3-positive cells in the striatal caudate nucleus, CA3 and dentate gyrus of the hippocampus, and thalamic medial nucleus (P < 0.05 vs. occlusion-vehicle). In the white matter tracts, recombinant human erythropoietin increased total, but not immature/mature oligodendrocytes (P < 0.05 vs. occlusion-vehicle), with increased cell proliferation and reduced induction of activated caspase-3, microglia and astrocytes (P < 0.05). Finally, occlusion-Epo reduced seizure burden, with more rapid recovery of electroencephalogram power, spectral edge frequency, and carotid blood flow. In summary, prolonged infusion of recombinant human erythropoietin after severe asphyxia in preterm fetal sheep was partially neuroprotective and improved electrophysiological and cerebrovascular recovery, in association with reduced apoptosis and inflammation.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1177/0271678X16650455</identifier><identifier>PMID: 27207167</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Asphyxia - drug therapy ; Electroencephalography - drug effects ; Erythropoietin - administration & dosage ; Erythropoietin - pharmacology ; Female ; Gray Matter - drug effects ; Humans ; Neurons - drug effects ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - pharmacology ; Original ; Pregnancy ; Sheep ; White Matter - drug effects</subject><ispartof>Journal of cerebral blood flow and metabolism, 2017-03, Vol.37 (3), p.1080-1094</ispartof><rights>The Author(s) 2016</rights><rights>The Author(s) 2016 2016 International Society for Cerebral Blood Flow and Metabolism</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-78d5516b7e9cb1c8ad86b7673057e9995ebf18c5f7df7cf1acefba32f3099b8b3</citedby><cites>FETCH-LOGICAL-c481t-78d5516b7e9cb1c8ad86b7673057e9995ebf18c5f7df7cf1acefba32f3099b8b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363482/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363482/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,21817,27922,27923,43619,43620,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27207167$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wassink, Guido</creatorcontrib><creatorcontrib>Davidson, Joanne O</creatorcontrib><creatorcontrib>Dhillon, Simerdeep K</creatorcontrib><creatorcontrib>Fraser, Mhoyra</creatorcontrib><creatorcontrib>Galinsky, Robert</creatorcontrib><creatorcontrib>Bennet, Laura</creatorcontrib><creatorcontrib>Gunn, Alistair J</creatorcontrib><title>Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep</title><title>Journal of cerebral blood flow and metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832.5 IU/h), starting 30 min after asphyxia and continued until 72 h. Recombinant human erythropoietin reduced neuronal loss and numbers of caspase-3-positive cells in the striatal caudate nucleus, CA3 and dentate gyrus of the hippocampus, and thalamic medial nucleus (P < 0.05 vs. occlusion-vehicle). In the white matter tracts, recombinant human erythropoietin increased total, but not immature/mature oligodendrocytes (P < 0.05 vs. occlusion-vehicle), with increased cell proliferation and reduced induction of activated caspase-3, microglia and astrocytes (P < 0.05). Finally, occlusion-Epo reduced seizure burden, with more rapid recovery of electroencephalogram power, spectral edge frequency, and carotid blood flow. In summary, prolonged infusion of recombinant human erythropoietin after severe asphyxia in preterm fetal sheep was partially neuroprotective and improved electrophysiological and cerebrovascular recovery, in association with reduced apoptosis and inflammation.</description><subject>Animals</subject><subject>Asphyxia - drug therapy</subject><subject>Electroencephalography - drug effects</subject><subject>Erythropoietin - administration & dosage</subject><subject>Erythropoietin - pharmacology</subject><subject>Female</subject><subject>Gray Matter - drug effects</subject><subject>Humans</subject><subject>Neurons - drug effects</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Original</subject><subject>Pregnancy</subject><subject>Sheep</subject><subject>White Matter - drug effects</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UU2L1TAUDaI4z9G9K8nSTTVpX5p0I8igM8KALhTchdv05jVDm9QkdXx_wV9tyhsHFVyFe77uJYeQ55y94lzK16yWvJXqK29bwfZCPCA7LkRXScbbh2S30dXGn5EnKd0wxlQjxGNyVsuabc4d-fkJYnYw0dvRZaTgB3qIeKQz5IyRLjFkNNkFT29dHrd5Cv6AA3XermnDg6URTZh758FnOq4zeIrxmMcYluAwO0_BbmGQlvH4w0HxliAs0Ewt5rI8jYjLU_LIwpTw2d17Tr68f_f54qq6_nj54eLtdWX2iudKqkEI3vYSO9Nzo2BQZWhlw0SBuk5gb7kywsrBSmM5GLQ9NLVtWNf1qm_OyZtT7rL2Mw4GfY4w6SW6GeJRB3D6b8a7UR_Cdy2attmrugS8vAuI4duKKevZJYPTBB7DmjRXdduqujRSpOwkNTGkFNHer-FMbxXqfysslhd_nndv-N1ZEVQnQYID6puwRl--6_-BvwBLnKnj</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Wassink, Guido</creator><creator>Davidson, Joanne O</creator><creator>Dhillon, Simerdeep K</creator><creator>Fraser, Mhoyra</creator><creator>Galinsky, Robert</creator><creator>Bennet, Laura</creator><creator>Gunn, Alistair J</creator><general>SAGE Publications</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170301</creationdate><title>Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep</title><author>Wassink, Guido ; Davidson, Joanne O ; Dhillon, Simerdeep K ; Fraser, Mhoyra ; Galinsky, Robert ; Bennet, Laura ; Gunn, Alistair J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-78d5516b7e9cb1c8ad86b7673057e9995ebf18c5f7df7cf1acefba32f3099b8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Asphyxia - drug therapy</topic><topic>Electroencephalography - drug effects</topic><topic>Erythropoietin - administration & dosage</topic><topic>Erythropoietin - pharmacology</topic><topic>Female</topic><topic>Gray Matter - drug effects</topic><topic>Humans</topic><topic>Neurons - drug effects</topic><topic>Neuroprotective Agents - administration & dosage</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Original</topic><topic>Pregnancy</topic><topic>Sheep</topic><topic>White Matter - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wassink, Guido</creatorcontrib><creatorcontrib>Davidson, Joanne O</creatorcontrib><creatorcontrib>Dhillon, Simerdeep K</creatorcontrib><creatorcontrib>Fraser, Mhoyra</creatorcontrib><creatorcontrib>Galinsky, Robert</creatorcontrib><creatorcontrib>Bennet, Laura</creatorcontrib><creatorcontrib>Gunn, Alistair 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cerebral blood flow and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wassink, Guido</au><au>Davidson, Joanne O</au><au>Dhillon, Simerdeep K</au><au>Fraser, Mhoyra</au><au>Galinsky, Robert</au><au>Bennet, Laura</au><au>Gunn, Alistair J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep</atitle><jtitle>Journal of cerebral blood flow and metabolism</jtitle><addtitle>J Cereb Blood Flow Metab</addtitle><date>2017-03-01</date><risdate>2017</risdate><volume>37</volume><issue>3</issue><spage>1080</spage><epage>1094</epage><pages>1080-1094</pages><issn>0271-678X</issn><eissn>1559-7016</eissn><abstract>Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832.5 IU/h), starting 30 min after asphyxia and continued until 72 h. Recombinant human erythropoietin reduced neuronal loss and numbers of caspase-3-positive cells in the striatal caudate nucleus, CA3 and dentate gyrus of the hippocampus, and thalamic medial nucleus (P < 0.05 vs. occlusion-vehicle). In the white matter tracts, recombinant human erythropoietin increased total, but not immature/mature oligodendrocytes (P < 0.05 vs. occlusion-vehicle), with increased cell proliferation and reduced induction of activated caspase-3, microglia and astrocytes (P < 0.05). Finally, occlusion-Epo reduced seizure burden, with more rapid recovery of electroencephalogram power, spectral edge frequency, and carotid blood flow. In summary, prolonged infusion of recombinant human erythropoietin after severe asphyxia in preterm fetal sheep was partially neuroprotective and improved electrophysiological and cerebrovascular recovery, in association with reduced apoptosis and inflammation.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>27207167</pmid><doi>10.1177/0271678X16650455</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Asphyxia - drug therapy Electroencephalography - drug effects Erythropoietin - administration & dosage Erythropoietin - pharmacology Female Gray Matter - drug effects Humans Neurons - drug effects Neuroprotective Agents - administration & dosage Neuroprotective Agents - pharmacology Original Pregnancy Sheep White Matter - drug effects |
| title | Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep |
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