dc.contributor.author |
Wassink, Guido |
|
dc.contributor.author |
Davidson, Joanne O |
|
dc.contributor.author |
Crisostomo, Alyssa |
|
dc.contributor.author |
Zhou, Kelly Q |
|
dc.contributor.author |
Galinsky, Robert |
|
dc.contributor.author |
Dhillon, Simerdeep K |
|
dc.contributor.author |
Lear, Christopher A |
|
dc.contributor.author |
Bennet, Laura |
|
dc.contributor.author |
Gunn, Alistair J |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2021-10-18T22:44:21Z |
|
dc.date.available |
2021-10-18T22:44:21Z |
|
dc.date.issued |
2021-1 |
|
dc.identifier.citation |
Brain communications 3(3):fcab172 Jan 2021 |
|
dc.identifier.issn |
2632-1297 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/57024 |
|
dc.description.abstract |
Therapeutic hypothermia for hypoxic-ischaemic encephalopathy provides partial white matter protection. Recombinant erythropoietin reduces demyelination after hypoxia-ischaemia, but it is unclear whether adjunct erythropoietin treatment can further improve outcomes after therapeutic hypothermia. Term-equivalent fetal sheep received sham-ischaemia (<i>n</i> = 9) or cerebral ischaemia for 30 min (ischaemia-vehicle, <i>n</i> = 8), followed by intravenous infusion of recombinant erythropoietin (ischaemia-Epo, <i>n</i> = 8; 5000 IU/kg bolus dose, then 833.3 IU/kg/h), cerebral hypothermia (ischaemia-hypothermia, <i>n</i> = 8), or recombinant erythropoietin plus hypothermia (ischaemia-Epo-hypothermia, <i>n</i> = 8), from 3 to 72 h post-ischaemia. Foetal brains were harvested at 7 days after cerebral ischaemia. Ischaemia was associated with marked loss of total Olig2-positive oligodendrocytes with reduced density of myelin and linearity of the white matter tracts (<i>P</i> < 0.01), and microglial induction and increased caspase-3-positive apoptosis. Cerebral hypothermia improved the total number of oligodendrocytes and restored myelin basic protein (<i>P</i> < 0.01), whereas recombinant erythropoietin partially improved myelin basic protein density and tract linearity. Both interventions suppressed microgliosis and caspase-3 (<i>P</i> < 0.05). Co-treatment improved 2',3'-cyclic-nucleotide 3'-phosphodiesterase-myelin density compared to hypothermia, but had no other additive effect. These findings suggest that although hypothermia and recombinant erythropoietin independently protect white matter after severe hypoxia-ischaemia, they have partially overlapping anti-inflammatory and anti-apoptotic effects, with little additive benefit of combination therapy. |
|
dc.format.medium |
Electronic-eCollection |
|
dc.language |
eng |
|
dc.publisher |
Oxford University Press (OUP) |
|
dc.relation.ispartofseries |
Brain communications |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
cerebral ischaemia |
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dc.subject |
erythropoietin |
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dc.subject |
foetal sheep |
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dc.subject |
hypothermia |
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dc.subject |
white matter |
|
dc.title |
Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1093/braincomms/fcab172 |
|
pubs.issue |
3 |
|
pubs.begin-page |
fcab172 |
|
pubs.volume |
3 |
|
dc.date.updated |
2021-09-04T00:28:18Z |
|
dc.rights.holder |
Copyright: The author |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/34409290 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
863234 |
|
dc.identifier.eissn |
2632-1297 |
|
dc.identifier.pii |
fcab172 |
|
pubs.online-publication-date |
2021-7-29 |
|