Preterm infants experience frequent arterial oxygen desaturations during oxygen therapy, or intermittent hypoxia (IH). 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 (n-3 PUFAs) combined with non-steroidal anti-inflammatory drugs (NSAIDs) is protective. Newborn rats were exposed to brief hypoxia (12% O₂) during hyperoxia (50% O₂) 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), n-3 PUFAs and/or topical ocular ketorolac. Placebo controls received daily oral olive oil and topical ocular saline. Room air (RA) littermates remained in 21% O₂ 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 n-3 PUFAs and n-3 PUFAs+CoQ10 with or without ketorolac. Neonatal IH was also associated with hemorrhage, oxidative stress, and elevations in inflammatory prostanoids. Supplementation with n-3 PUFAs and nGSH with and without ketorolac were most beneficial for myelin growth and integrity when administered in RA. However, the benefit of n-3 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 n-3 PUFAs suggest its susceptibility to oxidation in neonatal IH and therefore indicate that co-administration with antioxidants may be necessary to sustain its efficacy.

中文翻译：

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欧米茄 3 多不饱和脂肪酸、抗氧化剂和/或非甾体抗炎药对间歇性缺氧的新生大鼠大脑的影响

早产儿在氧疗或间歇性缺氧 (IH) 期间会频繁出现动脉氧饱和度降低。新生儿 IH 会增加氧化应激，从而导致神经炎症和脑损伤。我们测试了以下假设：接触新生儿 IH 对未成熟的大脑有害，早期补充抗氧化剂和/或欧米茄 3 多不饱和脂肪酸 ( n -3 PUFA) 与非甾体抗炎药 (NSAID) 相结合具有保护作用。新生大鼠暴露于短暂缺氧（12％氧气₂高氧期间）（50％氧气₂从寿命（P0）的第一天），直至在此期间他们每天接受口服补充抗氧化剂P14，即辅酶Q10（CoQ10的）或谷胱甘肽纳米粒子 (nGSH), n-3 PUFA 和/或局部眼用酮咯酸。安慰剂对照每天接受口服橄榄油和局部眼用盐水。室内空气 (RA) 同窝仔猪从出生到 P21保持在 21% O _{2 中}，所有处理均相同。在 P14 时，允许动物在 RA 中恢复至 P21，无需进一步治疗。收集全脑用于组织病理学和形态计量学分析，并评估氧化应激和炎症以及髓鞘损伤的生物标志物。新生儿 IH 导致更高的脑/体重比，这种效果被n -3 PUFAs 和n -3 PUFAs+CoQ10 与或不与酮咯酸逆转。新生儿 IH 还与出血、氧化应激和炎症性前列腺素升高有关。补充n-3 PUFAs 和 nGSH 和酮咯酸在 RA 中给药时对髓鞘生长和完整性最有益。然而，n -3 PUFA的益处在新生儿 IH 中显着减少。在大脑发育的关键时期，新生儿 IH 会导致炎症和氧化损伤。n -3 PUFA治疗益处的丧失表明其在新生儿 IH 中对氧化的敏感性，因此表明可能需要与抗氧化剂共同给药以维持其疗效。