A new model of neonatal stress which produces lasting neurobehavioral effects in adult rats
A new model of neonatal stress which produces lasting neurobehavioral effects in adult rats
复制标题
DOI：
10.1159/000100084
复制
发表时间：
2007-01-01
期刊：
影响因子：
2.5
通讯作者：
Juul, Sandra E.
中科院分区：
文献类型：
--
作者：
McPherson, Ronald J.;Gleason, Christine;Juul, Sandra E.
背景：在新生儿重症监护病房(NICU)的重症监护期间，婴儿经历了可能对成人健康产生持久影响的压力源和治疗。需要一个模拟NICU经历的动物模型来了解特定新生儿应激源的影响。目的：我们结合多种方法建立模拟NICU应激源的新生大鼠模型，以验证早期应激和硫酸吗啡(MS)暴露会影响发育和改变成年行为的假说。方法：幼鼠暴露于应激源，每日两次注射S(2 mg/kg)。连续5天(出生后3-7天)。应激包括每日母体分离(88.00~16.00h)、人工喂养、每日低氧/高氧发作(100%N-2 8min，然后100%O2 4min)和冷暴露(4摄氏度，每天20min)。共设5个处理组：(1)对照对照组(养坝和未处理)；(2)对照载体；(3)应激载体；(4)对照吗啡；(5)应激吗啡。测定早期生长发育指标。成人神经行为测试包括甩爪、被动回避和强迫游泳。测量新生儿多发性硬化症的药代动力学、新生儿和成人皮质酮水平、成人血细胞比容和血压。结果：新生儿应激显著增加病死率。新生儿应激和多发性硬化症治疗减缓了早期生长。新生儿多发性硬化症损害了被动回避学习，增加了强迫游泳的频率、持续时间和距离。皮质酮、红细胞压积或血压值没有差异。结论：该模型模拟NICU应激源，能够测量急性生理和长期神经行为指标。新生儿多发性硬化症的治疗损害了成人的认知功能。版权所有(C)2007 S.Karger AG，巴塞尔。
Background: During critical care in neonatal intensive care units ( NICU), infants experience stressors and treatments that may produce lasting effects on adult health. An animal model simulating the NICU experience is needed to understand the impact of specific neonatal stressors. Objective: We combined approaches to develop a neonatal rat model simulating NICU stressors in order to examine the hypothesis that early stress and morphine sulfate ( MS) exposure would affect development and alter adult behavior. Methods: Rat pups were exposed to stressors and given twice daily MS injections ( 2 mg/kg s. c.) for 5 days ( postnatal days 3 - 7). Stress included daily maternal separation ( from 08.00 to 16.00 h), hand feedings, a daily hypoxia/ hyperoxia episode ( 100% N-2 for 8 min, then 100% O-2 for 4 min), and cold exposure ( 4 degrees C for 20 min/ day). Five treatment groups were formed: ( 1) 'control control' ( dam reared and untreated); ( 2) control vehicle; ( 3) stress vehicle; ( 4) control morphine, and ( 5) stress morphine. Early growth and developmental indices were measured. Adult neurobehavioral tests were paw flick, passive avoidance, and forced swimming. Neonatal MS pharmacokinetics, neonatal and adult corticosterone levels, and adult hematocrit and blood pressure values were measured. Results: Neonatal stress significantly increased the mortality. Neonatal stress and MS treatment slowed early growth. Neonatal MS impaired passive avoidance learning and increased frequency, duration, and distance of forced swimming. There were no differences in corticosterone, hematocrit, or blood pressure values. Conclusions: This model simulates NICU stressors and enables measurement of acute physiological and long- term neurobehavioral indices. Neonatal MS treatment impaired the adult cognitive functioning. Copyright (c) 2007 S. Karger AG, Basel.