Fan Xiyong, van Bel Frank
Department of Neonatology, University Medical Center, Utrecht, The Netherlands.
J Matern Fetal Neonatal Med. 2010 Oct;23 Suppl 3:17-9. doi: 10.3109/14767058.2010.505052.
Recent progress has provided us with several promising neuroprotective compounds to reduce perinatal hypoxic-ischemic (HI) brain injury. In the early post HI phase, therapies can be concentrated on ion channel blockage (Xenon), anti-oxidation (allopurinol, 2-iminobiotin, and indomethacin), anti-inflammation (erythropoietin [EPO], melatonin), and anti-apoptosis (nuclear factor kappa B [NF-κB]and c-jun N-terminal kinase [JNK] inhibitors); in the later phase, therapies should be targeted to promote neuronal regeneration by stimulation of neurotrophic properties of the neonatal brain (EPO, growth factors, stem cells transplantation). Combination of pharmacological interventions with moderate hypothermia, which is the only established therapy for post HI brain injury, is probably the next step to fight HI brain damage in the clinical setting. Further studies should be concentrated on more rational pharmacological strategies by determining the optimal time and dose to inhibit the various potentially destructive molecular pathways and/or to enhance endogenous repair meanwhile avoiding the adverse effects.
近期的进展为我们提供了几种有前景的神经保护化合物,以减轻围产期缺氧缺血性(HI)脑损伤。在HI后的早期阶段,治疗可集中于离子通道阻断(氙气)、抗氧化(别嘌醇、2-亚氨基生物素和吲哚美辛)、抗炎(促红细胞生成素[EPO]、褪黑素)和抗凋亡(核因子κB[NF-κB]和c-jun氨基末端激酶[JNK]抑制剂);在后期阶段,治疗应旨在通过刺激新生脑的神经营养特性来促进神经元再生(EPO、生长因子、干细胞移植)。将药物干预与中度低温相结合,这是目前唯一已确立的HI后脑损伤治疗方法,可能是临床上对抗HI脑损伤的下一步措施。进一步的研究应集中于更合理的药物策略,即确定抑制各种潜在破坏性分子途径和/或增强内源性修复的最佳时间和剂量,同时避免不良反应。