Department of Neonatology, University Medical Center, Utrecht, the Netherlands.
Curr Neuropharmacol. 2010 Dec;8(4):324-34. doi: 10.2174/157015910793358150.
Perinatal hypoxia-ischemia (HI) is an important cause of neonatal brain injury. Recent progress in the search for neuroprotective compounds has provided us with several promising drugs to reduce perinatal HI-induced brain injury. In the early stage (first 6 hours after birth) therapies are concentrated on prevention of the production of reactive oxygen species or free radicals (xanthine-oxidase-, nitric oxide synthase-, and prostaglandin inhibition), anti-inflammatory effects (erythropoietin, melatonin, Xenon) and anti-apoptotic interventions (nuclear factor kappa B- and c-jun N-terminal kinase inhibition); in a later stage stimulation of neurotrophic properties in the neonatal brain (erythropoietin, growth factors) can be targeted to promote neuronal and oligodendrocyte regeneration. Combination of pharmacological means of treatment with moderate hypothermia, which is accepted now as a meaningful therapy, is probably the next step in clinical treatment to fight post-asphyxial brain damage. Further studies should be directed at a more rational use of therapies by determining the optimal time and dose to inhibit the different potentially destructive molecular pathways or to enhance endogenous repair while at the same time avoiding adverse effects of the drugs used.
围产期缺氧缺血（HI）是新生儿脑损伤的一个重要原因。寻找神经保护化合物的最新进展为我们提供了几种有希望的药物，以减少围产期 HI 引起的脑损伤。在早期（出生后 6 小时内），治疗集中在预防活性氧或自由基（黄嘌呤氧化酶、一氧化氮合酶和前列腺素抑制）的产生、抗炎作用（促红细胞生成素、褪黑素、氙气）和抗细胞凋亡干预（核因子 kappa B 和 c-jun N 末端激酶抑制）；在后期，可以针对新生儿大脑中的神经营养特性（促红细胞生成素、生长因子）进行刺激，以促进神经元和少突胶质细胞的再生。将治疗的药理手段与目前被认为有意义的亚低温治疗相结合，可能是治疗窒息后脑损伤的下一步临床治疗。进一步的研究应该通过确定抑制不同潜在破坏性分子途径的最佳时间和剂量，或增强内源性修复，同时避免所用药物的不良反应，来指导更合理地使用治疗方法。
