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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 (n\u2009=\u20099) or cerebral ischaemia for 30\u2009min (ischaemia-vehicle, n\u2009=\u20098), followed by intravenous infusion of recombinant erythropoietin (ischaemia-Epo, n\u2009=\u20098; 5000\u2009IU\/kg bolus dose, then 833.3\u2009IU\/kg\/h), cerebral hypothermia (ischaemia-hypothermia, n\u2009=\u20098), or recombinant erythropoietin plus hypothermia (ischaemia-Epo-hypothermia, n\u2009=\u20098), from 3 to 72\u2009h post-ischaemia. Foetal brains were harvested at 7\u2009days 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 (P\u2009&amp;lt;\u20090.01), and microglial induction and increased caspase-3-positive apoptosis. Cerebral hypothermia improved the total number of oligodendrocytes and restored myelin basic protein (P\u2009&amp;lt;\u20090.01), whereas recombinant erythropoietin partially improved myelin basic protein density and tract linearity. Both interventions suppressed microgliosis and caspase-3 (P\u2009&amp;lt;\u20090.05). Co-treatment improved 2\u2032,3\u2032-cyclic-nucleotide 3\u2032-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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab172","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T11:13:58Z","timestamp":1627470838000},"source":"Crossref","is-referenced-by-count":27,"title":["Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep"],"prefix":"10.1093","volume":"3","author":[{"given":"Guido","family":"Wassink","sequence":"first","affiliation":[{"name":"Department of Physiology, The University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne O","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department 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