Pharmacological neuroprotection after perinatal hypoxic-ischemic brain injury.
Pharmacological neuroprotection after perinatal hypoxic-ischemic brain injury.
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DOI：
10.2174/157015910793358150
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发表时间：
2010-12
影响因子：
5.3
通讯作者：
van Bel F
中科院分区：
文献类型：
--
作者：
Fan X;Kavelaars A;Heijnen CJ;Groenendaal F;van Bel F
围产期缺氧缺血（HI）是新生儿脑损伤的重要原因。最近在寻找神经保护化合物方面的进展为我们提供了几种有前途的药物来减少围产期HI诱导的脑损伤。在前期（出生后前6小时）治疗集中在预防活性氧或自由基的产生（黄嘌呤氧化酶、一氧化氮合酶和前列腺素抑制），抗炎作用（促红细胞生成素、褪黑激素、氙）和抗凋亡干预（核因子κ B-和c-jun N-末端激酶抑制）;在后期，可以靶向刺激新生儿脑中的神经营养特性（促红细胞生成素、生长因子）以促进神经元和少突胶质细胞再生。药物治疗手段与中度低温相结合，现在被认为是一种有意义的治疗方法，可能是对抗窒息后脑损伤的临床治疗的下一步。进一步的研究应通过确定最佳时间和剂量来抑制不同的潜在破坏性分子途径或增强内源性修复，同时避免所用药物的不良反应，从而更合理地使用治疗。
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.