Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia.
Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia.
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DOI：
10.1016/j.expneurol.2020.113442
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发表时间：
2020-12
影响因子：
5.3
通讯作者：
Stonestreet BS
中科院分区：
文献类型：
--
作者：
Schuffels S;Nakada S;Wu Y;Lim YP;Chen X;Stonestreet BS
缺氧缺血性脑损伤是早产儿和足月儿围产期并发症后最常见的神经系统疾病之一。低温是唯一被批准用于新生儿HI脑病的治疗方法。然而，这种治疗仅具有部分保护作用，不能用于治疗早产儿，并且对治疗严重HI脑病的疗效有限。新生儿HI脑损伤的发展与炎症有关。α间抑制蛋白（IAIP）是新生大鼠暴露于中度HI后具有神经保护特性的免疫调节蛋白。本研究的目的是确定在暴露于持续时间为120分钟的严重HI后立即开始或延迟1小时开始IAIP治疗的神经保护功效。将146只7日龄幼鼠随机分为假手术对照组、HI组和IAIP（60 mg/kg）或安慰剂（PL）立即治疗组，以及假手术组、HI组和IAIP或PL延迟治疗组。在HI后0、24和48小时或HI后1、24和48小时给予IAIP或PL。暴露于HI后72小时测定总脑梗死体积。在HI后立即给予IAIP治疗，雄性和雌性新生大鼠的梗死体积分别减少58.0%和44.5%（P<0.05）。HI后延迟IAIP治疗可使雄性大鼠的梗死体积减少23.7%（P<0.05），但对雌性大鼠无影响。我们得出结论，IAIPs发挥神经保护作用，即使暴露于严重HI新生大鼠，并出现一些性别相关的差异性影响。
Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in premature and full-term infants after perinatal complications. Hypothermia is the only treatment approved for HI encephalopathy in newborns. However, this treatment is only partially protective, cannot be used to treat premature infants, and has limited efficacy to treat severe HI encephalopathy. Inflammation contributes to the evolution of HI brain injury in neonates. Inter-alpha Inhibitor Proteins (IAIPs) are immunomodulatory proteins that have neuroprotective properties after exposure to moderate HI in neonatal rats. The objective of the current study was to determine the neuroprotective efficacy of treatment with IAIPs starting immediately after or with a delay of one hour after exposure to severe HI of 120 minutes duration. One hundred and forty-six 7-day-old rat pups were randomized to sham control, HI and immediate treatment with IAIPs (60 mg/kg) or placebo (PL), and sham, HI and delayed treatment with IAIPs or PL. IAIPs or PL were given at zero, 24, and 48 hours after HI or 1, 24 and 48 hours after HI. Total brain infarct volume was determined 72 hours after exposure to HI. Treatment with IAIPs immediately after HI decreased (P<0.05) infarct volumes by 58.0% and 44.5% in male and female neonatal rats, respectively. Delayed treatment with IAIPs after HI decreased (P<0.05) infarct volumes by 23.7% in male, but not in female rats. We conclude that IAIPs exert neuroprotective effects even after exposure to severe HI in neonatal rats and appear to exhibit some sex-related differential effects.
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