{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:34:19Z","timestamp":1764783259895,"version":"build-2065373602"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,3,14]],"date-time":"2011-03-14T00:00:00Z","timestamp":1300060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Erythropoietin (EPO) is a cytokine hormone with cytoprotective effects in many tissues including the brain. Although the benefits of administration of recombinant human EPO (rhEPO) for neonatal hypoxic brain injury have been demonstrated in neuronal tissue, the effect on non\u2010neuronal cell populations is unclear. We tested the hypothesis that rhEPO would not only protect neuronal cells but also glial cells at a stage of brain development where their maturation was particularly sensitive, and also protect the vasculature. This was evaluated in a rat model of hypoxic injury. 1000 IU\/kg rhEPO was delivered intraperitoneally at the start of 4 h hypoxia or normoxia. Treatment groups of neonatal rats (day of birth, at least <jats:italic>N<\/jats:italic> = 10 per group) were as follows: normoxia; normoxia plus rhEPO; hypoxia (8% FiO<jats:sub>2<\/jats:sub> delivered in temperature\u2010controlled chambers); and hypoxia plus rhEPO. Day of birth in rats is equivalent to human gestation of 28\u201332 weeks. The effects of rhEPO administration, especially to non\u2010neuronal cell populations, and the associated molecular pathways, were investigated. Apoptosis was increased with hypoxia and this was significantly reduced with rhEPO (<jats:italic>p<\/jats:italic> &lt; 0.05). The neuronal marker, microtubule\u2010associated protein\u20102, increased in expression (<jats:italic>p<\/jats:italic> &lt; 0.05) when apoptosis was significantly reduced by rhEPO. In addition, compared with hypoxia alone, rhEPO\u2010treated hypoxia had the following significant protein expression increases (<jats:italic>p<\/jats:italic> &lt; 0.05): the intermediate filament structural protein nestin; myelin basic protein (oligodendrocytes); and glial fibrillary acidic protein (astrocytes). In conclusion, rhEPO protects the developing brain via anti\u2010apoptotic mechanisms and promotes the health of non\u2010neuronal as well as neuronal cell populations at a time when loss of these cells would have long\u2010lasting effects on brain function. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2862","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T09:14:31Z","timestamp":1296724471000},"page":"101-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Erythropoietin protects against apoptosis and increases expression of non\u2010neuronal cell markers in the hypoxia\u2010injured developing brain"],"prefix":"10.1002","volume":"224","author":[{"given":"Miko","family":"Yamada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Burke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Colditz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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