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Neonatal IH increases oxidative distress which contributes to neuroinflammation and brain injury. We tested the hypotheses that exposure to neonatal IH is detrimental to the immature brain and that early supplementation with antioxidants and\/or omega 3 polyunsaturated fatty acids (<jats:italic>n<\/jats:italic>\u20103 PUFAs) combined with non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) is protective. Newborn rats were exposed to brief hypoxia (12% O<jats:sub>2<\/jats:sub>) during hyperoxia (50% O<jats:sub>2<\/jats:sub>) from the first day of life (P0) until P14 during which they received daily oral supplementation with antioxidants, namely coenzyme Q10 (CoQ10) or glutathione nanoparticles (nGSH), <jats:italic>n<\/jats:italic>\u20103 PUFAs and\/or topical ocular ketorolac. Placebo controls received daily oral olive oil and topical ocular saline. Room air (RA) littermates remained in 21% O<jats:sub>2<\/jats:sub> from birth to P21 with all treatments identical. At P14 animals were allowed to recover in RA until P21 with no further treatment. Whole brains were harvested for histopathology and morphometric analyses, and assessed for biomarkers of oxidative stress and inflammation, as well as myelin injury. Neonatal IH resulted in higher brain\/body weight ratios, an effect that was reversed with <jats:italic>n<\/jats:italic>\u20103 PUFAs and <jats:italic>n<\/jats:italic>\u20103 PUFAs+CoQ10 with or without ketorolac. Neonatal IH was also associated with hemorrhage, oxidative stress, and elevations in inflammatory prostanoids. Supplementation with <jats:italic>n<\/jats:italic>\u20103 PUFAs and nGSH with and without ketorolac were most beneficial for myelin growth and integrity when administered in RA. However, the benefit of <jats:italic>n<\/jats:italic>\u20103 PUFAs was significantly curtailed in neonatal IH. Neonatal IH during a critical time of brain development causes inflammation and oxidative injury. Loss of therapeutic benefits of <jats:italic>n<\/jats:italic>\u20103 PUFAs suggest its susceptibility to oxidation in neonatal IH and therefore indicate that co\u2010administration with antioxidants may be necessary to sustain its efficacy.<\/jats:p>","DOI":"10.1002\/jdn.10120","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T06:25:42Z","timestamp":1620627942000},"page":"448-460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of omega 3 polyunsaturated fatty acids, antioxidants, and\/or non\u2010steroidal inflammatory drugs in the brain of neonatal rats exposed to intermittent hypoxia"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7008-5498","authenticated-orcid":false,"given":"Alex","family":"Manlapaz\u2010Mann","sequence":"first","affiliation":[{"name":"Department of Pediatrics State University of New York Downstate Medical Center  Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles L.","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Neonatal\u2010Perinatal Medicine State University of New York Downstate Medical Center  Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8834-5238","authenticated-orcid":false,"given":"Darren","family":"Bodkin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics State University of New York Downstate Medical Center  Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghassan","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Neonatal\u2010Perinatal Medicine State University of New York Downstate Medical Center  Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob V.","family":"Aranda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Neonatal\u2010Perinatal Medicine State University of New York Downstate Medical Center  Brooklyn NY USA"},{"name":"Department of Ophthalmology State University of New York Downstate Medical Center  Brooklyn NY USA"},{"name":"SUNY Eye Institute  Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4129-475X","authenticated-orcid":false,"given":"Kay D.","family":"Beharry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Neonatal\u2010Perinatal Medicine State University of New York Downstate Medical Center  Brooklyn NY USA"},{"name":"Department of Ophthalmology State University of New York Downstate Medical Center  Brooklyn NY USA"},{"name":"SUNY Eye Institute  Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4468-06.2007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20832"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.105"},{"key":"e_1_2_10_5_1","first-page":"241","article-title":"The effects of omega 3 fatty acid supplementation on brain tissue oxidative status in aged Wistar rats","volume":"16","author":"Avramovic N.","year":"2012","journal-title":"Hippokratia"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230490465874"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox6040103"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox7110160"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033712"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1705-2"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903550208"},{"key":"e_1_2_10_12_1","first-page":"218","article-title":"Chronic intermittent hypoxia causes lipid peroxidation and altered phase 1 drug metabolizing enzymes in the neonatal rat liver","volume":"3","author":"Cai C.","year":"2017","journal-title":"React Oxyg Species (Apex)"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2831"},{"key":"e_1_2_10_14_1","first-page":"505","article-title":"Effects of dl\u20103\u2010n\u2010butylphthalide on production of TXB2 and 6\u2010keto\u2010PGF1 alpha in rat brain during focal cerebral ischemia and reperfusion","volume":"18","author":"Chong Z. 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