Human brain lesions in the perinatal period result in life-long neuro-disabilities impairing sensory-motor, cognitive, and behavior functions for years. Topographical aspects of brain lesions depend on gestational age at the time of insult in preterm or term infants and impaired subsequent steps of brain development and maturation. In mice, the Rice-Vannucci procedure of neonate hypoxia-ischemia (HI) was used at 5 days (P5) or P10, mimicking the development of 30 week-gestation fetus/preterm newborn, or full-term infant, respectively. Transcription response to HI was assessed at 3, 6, 12, and 24 h after insult, using micro-array technology. Statistical Pathway and Gene Ontology terms enrichments were investigated using DAVID^®, Revigo^® and Ingenuity Pathway Analysis (IPA^®) to identify a core of transcription response to HI, age-specific regulations, and interactions with spontaneous development. Investigations were based on direction, amplitude, and duration of responses, basal expression, and annotation. Five major points deserve attention; (i) inductions exceeded repressions (60/40%) at both ages, (ii) only 20.3% (393/1938 records) were common to P5 and P10 mice, (iii) at P5, HI effects occurred early and decreased 24 h after insult whereas they were delayed at P10 and increased 24 h after insult, (iv) common responses at P5 and P10 involved inflammation, immunity, apoptosis, and angiogenesis. (v) age-specific effects occurred with higher statistical significance at P5 than at P10. Transient repression of 12 genes encoding cholesterol biosynthesis enzymes was transiently observed 12 h after HI at P5. Synaptogenesis appeared inhibited at P5 while induced at P10, showing reciprocal effects on glutamate receptors. Specific involvement of Il-1 (interleukin-1) implicated in the firing of inflammation was observed at P10. This study pointed out age-differences in HI responses kinetics, e.g., a long-lasting inflammatory response at P10 compared to P5. Whether the specific strong depression of cholesterol biosynthesis genes that could account for white matter-specific vulnerability at P5 or prevent delayed inflammation needs further investigation. Determination of putative involvement of Il-1 and the identification of upstream regulators involved in the delayed inflammation firing at P10 appears promising routes of research in the understandings of age-dependent vulnerabilities in the neonatal brain.

围产期的人类大脑损伤会导致终生神经障碍，多年来损害感觉运动、认知和行为功能。脑损伤的地形方面取决于早产儿或足月婴儿受到损伤时的胎龄以及随后的脑发育和成熟步骤受损。在小鼠中，新生儿缺氧缺血 (HI) 的 Rice-Vannucci 程序在第 5 天 (P5) 或 P10 时使用，分别模拟 30 周妊娠胎儿/早产新生儿或足月婴儿的发育。使用微阵列技术在损伤后 3、6、12 和 24 小时评估对 HI 的转录反应。使用 DAVID ^® 、 Revigo ^®和 Ingenuity Pathway Analysis (IPA ^® ) 对统计通路和基因本体术语富集进行了研究，以确定对 HI、年龄特异性调节以及与自发发育的相互作用的转录反应的核心。调查基于反应的方向、幅度和持续时间、基础表达和注释。五个要点值得关注； (i) 两个年龄段的诱导均超过抑制 (60/40%)，(ii) P5 和 P10 小鼠中只有 20.3%（393/1938 条记录）常见，(iii) 在 P5 时，HI 效应较早发生并在 24 小时内降低(iv) P5 和 P10 的常见反应涉及炎症、免疫、细胞凋亡和血管生成。 (v) P5 时的年龄特异性效应比 P10 时具有更高的统计显着性。在 P5 HI 后 12 小时，短暂观察到编码胆固醇生物合成酶的 12 个基因的短暂抑制。突触发生在 P5 时似乎受到抑制，而在 P10 时被诱导，显示出对谷氨酸受体的相互作用。 在 P10 时观察到与炎症激发有关的 Il-1（白介素-1）的特异性参与。这项研究指出了 HI 反应动力学的年龄差异，例如，与 P5 相比，P10 时的炎症反应持续时间较长。胆固醇生物合成基因的特异性强烈抑制是否可以解释 P5 期白质特异性脆弱性或预防迟发性炎症，需要进一步研究。确定 IL-1 的假定参与以及鉴定参与 P10 延迟炎症激发的上游调节因子似乎是了解新生儿大脑年龄依赖性脆弱性的有希望的研究途径。