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Early Versus Late Caffeine and/or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for Prevention of Intermittent Hypoxia Induced Neuroinflammation in the Neonatal Rat
Batool, M.; Cai, C.L.; Aranda, J.V.; Hand, I.; Beharry, K.D. Early versus Late Caffeine and/or Non‐steroidal Anti‐inflammatory Drugs (NSAIDS) for Prevention of Intermittent Hypoxia‐induced Neuroinflammation in the Neonatal Rat. International Journal of Developmental Neuroscience 2024, doi:10.1002/jdn.10321.
Batool, M.; Cai, C.L.; Aranda, J.V.; Hand, I.; Beharry, K.D. Early versus Late Caffeine and/or Non‐steroidal Anti‐inflammatory Drugs (NSAIDS) for Prevention of Intermittent Hypoxia‐induced Neuroinflammation in the Neonatal Rat. International Journal of Developmental Neuroscience 2024, doi:10.1002/jdn.10321.
Batool, M.; Cai, C.L.; Aranda, J.V.; Hand, I.; Beharry, K.D. Early versus Late Caffeine and/or Non‐steroidal Anti‐inflammatory Drugs (NSAIDS) for Prevention of Intermittent Hypoxia‐induced Neuroinflammation in the Neonatal Rat. International Journal of Developmental Neuroscience 2024, doi:10.1002/jdn.10321.
Batool, M.; Cai, C.L.; Aranda, J.V.; Hand, I.; Beharry, K.D. Early versus Late Caffeine and/or Non‐steroidal Anti‐inflammatory Drugs (NSAIDS) for Prevention of Intermittent Hypoxia‐induced Neuroinflammation in the Neonatal Rat. International Journal of Developmental Neuroscience 2024, doi:10.1002/jdn.10321.
Abstract
Preterm infants often experience frequent intermittent hypoxia (IH) episodes which is associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non-steroidal in-flammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH-induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hy-peroxia (50% O2) from birth (P0) to P14. For early treatment, the pups were administered: 1) dai-ly caffeine citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1-P14); 2) ke-torolac topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) caffeine+ketorolac co-treatment; 5) caffeine+ibuprofen co-treatment; or 6) equivalent volume saline. On P14, animals were placed in room air (RA) with no further treatment. For late treatment, pups received similar treatments from P15-P21 (caffeine and/or ketorolac), or P15-P17 (ibuprofen). RA control were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, mye-lination, and biomarkers of inflammation. IH caused significant inflammation, reduced mye-lination, and apoptosis in preterm rat brains, an effect that was improved predominantly with combined caffeine/NSAID early treatment. Early caffeine/NSAID co-treatment confers syner-gistic neuroprotection against IH-induced damage.
Biology and Life Sciences, Neuroscience and Neurology
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