Benesová O, Tejkalová H, Kristofiková Z, Dostál M, Husek P
Psychiatrické centrum, Praha.
Cesk Fysiol. 1995 Mar;44(1):11-4.
Perinatal period, which is characterized by intensive histogenesis and cytodifferentiation of the already shaped organs, is a highly vulnerable phase for fetal/neonatal brain and immune system-organs with high similarity in receptor equipment. Even fine deviations in the programmed developmental processes induced by drugs initiate disorders in the formation of neural network, cytoarchitectonics and receptor-transmitter communication systems. This pathology is not evident at birth, but forms the basis for various functional defects of neuro-psycho-immunocompetence which become apparent gradually during further maturation or even in adulthood. Clinical recognition of such functional teratogenic action of drugs is hampered by the long time interval (upto decades) between the drug administration and its consequences, making the identification of causal relations very difficult. Consequently, experimental research is necessary under the precondition of adequate animal models with sufficient validity for the extrapolation on human level. The authors suggest the principles of such approach using drug application in neonatal rats with lifelong follow-up of behaviour, immune reactivity and brain biochemical analysis. The evaluation of functional teratogenic risk in three drugs used in the treatment of risk pregnancies and risk neonates (dexamethazone, fenoterol, diazepam) is presented.
围产期的特点是已形成的器官进行密集的组织发生和细胞分化，这对胎儿/新生儿的大脑和免疫系统器官来说是一个高度脆弱的阶段，这些器官在受体装备方面具有高度相似性。即使是药物引起的程序性发育过程中的细微偏差，也会引发神经网络、细胞结构和受体-递质通讯系统形成的紊乱。这种病理现象在出生时并不明显，但却是神经-心理-免疫能力各种功能缺陷的基础，这些缺陷在进一步成熟过程中甚至在成年期会逐渐显现出来。药物这种功能性致畸作用的临床识别受到药物给药与其后果之间长时间间隔（长达数十年）的阻碍，这使得确定因果关系非常困难。因此，在具有足够有效性以推断人类情况的适当动物模型的前提下，进行实验研究是必要的。作者提出了这种方法的原则，即在新生大鼠中使用药物并对其行为、免疫反应性和脑生化分析进行终身随访。本文介绍了对用于治疗高危妊娠和高危新生儿的三种药物（地塞米松、非诺特罗、地西泮）的功能性致畸风险评估。
