Neonatal hypoxia-ischemia (HI) is among the main causes of mortality and morbidity in newborns. Experimental studies show that the immature rat brain is less susceptible to HI injury, suggesting that changes that occur during the first days of life drastically alter its susceptibility. Among the main developmental changes observed is the mitochondrial function, namely, the tricarboxylic acid (TCA) cycle and respiratory complex (RC) activities. Therefore, in the present study, we investigated the influence of neonatal HI on mitochondrial functions, redox homeostasis, and cell damage at different postnatal ages in the hippocampus of neonate rats. For this purpose, animals were divided into four groups: sham postnatal day 3 (ShP3), HIP3, ShP11, and HIP11. We initially observed increased apoptosis in the HIP11 group only, indicating a higher susceptibility of these animals to brain injury. Mitochondrial damage, as determined by flow cytometry showing mitochondrial swelling and loss of mitochondrial membrane potential, was also demonstrated only in the HIP11 group. This was consistent with the decreased mitochondrial oxygen consumption, reduced TCA cycle enzymes, and RC activities and induction of oxidative stress in this group of animals. Considering that HIP3 and the sham animals showed no alteration of mitochondrial functions, redox homeostasis, and showed no apoptosis, our data suggest an age-dependent vulnerability of the hippocampus to hypoxia-ischemia. The present results highlight age-dependent metabolic differences in the brain of neonate rats submitted to HI indicating that different treatments might be needed for HI newborns with different gestational ages.

新生儿缺氧缺血（HI）是新生儿死亡和发病的主要原因之一。实验研究表明，未成熟的大鼠大脑不太容易受到 HI 损伤，这表明在生命最初几天发生的变化会极大地改变其易感性。观察到的主要发育变化是线粒体功能，即三羧酸 (TCA) 循环和呼吸复合物 (RC) 活动。因此，在本研究中，我们研究了新生儿 HI 对新生大鼠海马不同出生年龄阶段线粒体功能、氧化还原稳态和细胞损伤的影响。为此，将动物分为四组：假产后第 3 天 (ShP3)、HIP3、ShP11 和 HIP11。我们最初仅观察到 HIP11 组细胞凋亡增加，表明这些动物对脑损伤的敏感性更高。流式细胞仪测定显示线粒体肿胀和线粒体膜电位丧失的线粒体损伤也仅在 HIP11 组中得到证实。这与这组动物中线粒体耗氧量减少、TCA 循环酶减少、RC 活性和氧化应激诱导一致。考虑到 HIP3 和假动物没有表现出线粒体功能、氧化还原稳态的改变，也没有表现出细胞凋亡，我们的数据表明海马体对缺氧缺血的脆弱性与年龄有关。