Prenatal and early postnatal periods are important for brain development and neural function. Neonatal insults such as hypoxia-ischemia (HI) causes prolonged neural and metabolic dysregulation, affecting central nervous system maturation. There is evidence that brain hypometabolism could increase the risk of adult-onset neurodegenerative diseases. However, the impact of non-pharmacologic strategies to attenuate HI-induced brain glucose dysfunction is still underexplored. This study investigated the long-term effects of early environmental enrichment in metabolic, cell, and functional responses after neonatal HI. Thereby, male Wistar rats were divided according to surgical procedure, sham, and HI (performed at postnatal day 3), and the allocation to standard (SC) or enriched condition (EC) during gestation and lactation periods. In-vivo cerebral metabolism was assessed by means of [¹⁸F]-FDG micro-positron emission tomography, and cognitive, biochemical, and histological analyses were performed in adulthood. Our findings reveal that HI causes a reduction in glucose metabolism and glucose transporter levels as well as hyposynchronicity in metabolic brain networks. However, EC during prenatal or early postnatal period attenuated these metabolic disturbances. A positive correlation was observed between [¹⁸F]-FDG values and volume ratios in adulthood, indicating that preserved tissue by EC is metabolically active. EC promotes better cognitive scores, as well as down-regulation of amyloid precursor protein in the parietal cortex and hippocampus of HI animals. Furthermore, growth-associated protein 43 was up-regulated in the cortex of EC animals. Altogether, results presented support that EC during gestation and lactation period can reduce HI-induced impairments that may contribute to functional decline and progressive late neurodegeneration.

中文翻译：

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产前和产后早期丰富的环境体验通过代谢和神经可塑性机制预防新生儿缺氧缺血晚期神经变性

产前和产后早期对大脑发育和神经功能很重要。新生儿损伤如缺氧缺血 (HI) 会导致长期的神经和代谢失调，影响中枢神经系统的成熟。有证据表明，脑代谢减退可能会增加成人发病的神经退行性疾病的风险。然而，非药物策略对减轻 HI 诱导的脑葡萄糖功能障碍的影响仍未得到充分探索。本研究调查了早期环境富集对新生儿 HI 后代谢、细胞和功能反应的长期影响。因此，雄性 Wistar 大鼠根据手术程序、假手术和 HI（在出生后第 3 天进行）以及在妊娠和哺乳期间分配到标准 (SC) 或富集条件 (EC) 进行划分。¹⁸ F]-FDG 微正电子发射断层扫描以及认知、生化和组织学分析在成年期进行。我们的研究结果表明，HI 导致葡萄糖代谢和葡萄糖转运蛋白水平降低以及代谢脑网络的低同步性。然而，产前或产后早期的 EC 减轻了这些代谢紊乱。[ ¹⁸F]-FDG 值和成年期的体积比，表明 EC 保存的组织具有代谢活性。EC 促进更好的认知评分，以及 HI 动物顶叶皮层和海马中淀粉样前体蛋白的下调。此外，生长相关蛋白 43 在 EC 动物的皮层中上调。总之，结果表明妊娠和哺乳期的 EC 可以减少 HI 诱导的损伤，这些损伤可能导致功能下降和进行性晚期神经变性。