Fiedorowicz Michał, Makarewicz Dorota, Stańczak-Mrozek Kinga I, Grieb Paweł
Department of Experimental Pharmacology, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Acta Neurobiol Exp (Wars). 2008;68(3):389-97. doi: 10.55782/ane-2008-1705.
To estimate protective potential of citicoline in a model of birth asphyxia, the drug was given to 7-day old rats subjected to permanent unilateral carotid artery occlusion and exposed for 65 min to a hypoxic gas mixture. Daily citicoline doses of 100 or 300 m/kg, or vehicle, were injected intraperitoneally for 7 consecutive days beginning immediately after the end of the ischemic-hypoxic insult, and brain damage was assessed by gross zorphology score and weight deficit two weeks after the insult. Caspase-3, alpha-fodrin, Bcl-2, and Hsp70 levels were assessed at 0, 1, and 24 h after the end of the hypoxic insult in another group of rat pups subjected to the same insult and given a single dose of 300 m/kg of citicoline or the vehicle. Citicoline markedly reduced caspase-3 activation and Hsp70 expression 24 h after the insult, and dose-dependently attenuated brain damage. In the context of the well-known excellent safety profile of citicoline, these data suggest that clinical evaluation of the efficacy of the drug in human birth asphyxia may be warranted.
为评估胞磷胆碱在新生儿窒息模型中的保护潜力，将该药物给予7日龄大鼠，这些大鼠接受永久性单侧颈动脉闭塞，并暴露于低氧混合气体中65分钟。从缺血缺氧损伤结束后立即开始，连续7天腹腔注射每日剂量为100或300mg/kg的胞磷胆碱或赋形剂，损伤两周后通过大体形态学评分和重量减轻评估脑损伤。在另一组遭受相同损伤并给予单剂量300mg/kg胞磷胆碱或赋形剂的幼鼠中，在缺氧损伤结束后的0、1和24小时评估半胱天冬酶-3、α- fodrin、Bcl-2和Hsp70水平。胞磷胆碱在损伤后24小时显著降低半胱天冬酶-3激活和Hsp70表达，并剂量依赖性减轻脑损伤。鉴于胞磷胆碱具有众所周知的良好安全性，这些数据表明该药物在人类新生儿窒息中的疗效可能值得进行临床评估。
