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We tested the hypotheses that early caffeine and\/or non\u2010steroidal inflammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH\u2010induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hyperoxia (50% O<jats:sub>2<\/jats:sub>) from birth (P0) to P14. For early treatment, the pups were administered: 1) daily caffeine (Caff) citrate (Cafcit, 20\u2009mg\/kg IP loading on P0, followed by 5\u00a0mg\/kg from P1\u2010P14); 2) ketorolac (Keto) topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Ibu, Neoprofen, 10\u00a0mg\/kg loading dose on P0 followed by 5\u00a0mg\/kg\/day on P1 and P2); 4) Caff+Keto co\u2010treatment; 5) Caff+Ibu co\u2010treatment; or 6) equivalent volume saline (Sal). On P14, animals were placed in room air (RA) with no further treatment until P21. For late treatment, pups were exposed from P0 to P14, then placed in RA during which they received similar treatments from P15\u2010P21 (Sal, Caff, and\/or Keto), or P15\u2010P17 (Ibu). RA controls were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, myelination, and biomarkers of inflammation. IH caused significant brain injury and hemorrhage, inflammation, reduced myelination, and apoptosis. Early treatment with Caff alone or in combination with NSAIDs conferred better neuroprotection against IH\u2010induced damage than late treatment. Early postnatal treatment during a critical time of brain development, may be preferable for the prevention of IH\u2010induced brain injury in preterm infants.<\/jats:p>","DOI":"10.1002\/jdn.10321","type":"journal-article","created":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T07:18:30Z","timestamp":1709968710000},"page":"227-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early versus late caffeine and\/or non\u2010steroidal anti\u2010inflammatory drugs (NSAIDS) for prevention of intermittent hypoxia\u2010induced neuroinflammation in the neonatal rat"],"prefix":"10.1002","volume":"84","author":[{"given":"Myra","family":"Batool","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatal\u2010Perinatal Medicine, State University of New York Downstate Health Sciences University  Brooklyn NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles 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