Effects of tapering neonatal dexamethasone on rat growth, neurodevelopment, and stress response
Effects of tapering neonatal dexamethasone on rat growth, neurodevelopment, and stress response
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DOI：
10.1152/ajpregu.2002.282.1.r55
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发表时间：
2002-01-01
影响因子：
2.8
通讯作者：
Neal, CR
中科院分区：
文献类型：
--
作者：
Flagel, SB;V치zquez, DM;Neal, CR
地塞米松通常用于减少早产儿慢性肺病的发病率，但对其长期使用的神经系统后果知之甚少。为了研究地塞米松对神经系统的影响，我们建立了一个大鼠模型，在该模型中，新生幼鼠在新生儿重症监护病房中暴露于相应的神经发育时间，逐渐减少剂量的地塞米松。在产后第2天（PD），将窝鼠分为3组：1)处理对照组，2)注射盐水组，3)在PD 3至PD 6期间逐渐剂量注射地塞米松肌注组。地塞米松治疗的动物体生长和脑重量均下降。地塞米松治疗的动物在PD 7和PD 14中表现出总体神经发育的延迟，但在PD 20中没有。在青春期晚期（PD 33），地塞米松治疗的动物在光明和黑暗环境中活动较少，同时对新压力表现出迟钝的血清皮质酮反应。行为应激反应和激素应激反应之间的分离表明，新生儿地塞米松暴露会永久性地改变中枢神经系统功能，特别是在神经内分泌应激轴内。这可能会导致学习障碍和对环境反应不良的风险增加。
Dexamethasone is commonly used to lessen the morbidity of chronic lung disease in premature infants, but little is known regarding neurological consequences of its prolonged use. To study neurological effects of dexamethasone, we have developed a rat model in which newborn pups are exposed to tapering doses of dexamethasone at a time corresponding neurodevelopmentally to human exposure in the neonatal intensive care unit. On postnatal day (PD) 2, litters were divided into three groups: 1) handled controls, 2) saline-injected animals, and 3) animals injected with tapering doses of intramuscular dexamethasone between PD 3 and 6. Somatic growth and brain weight were decreased in dexamethasone-treated animals. Dexamethasone-treated animals demonstrated delays in gross neurological development on PD 7 and 14 but not PD 20. In late adolescence (PD 33), dexamethasone-treated animals were less active in light and dark environments, while demonstrating a blunted serum corticosterone response to a novel stress. The dissociation between behavioral and hormonal stress responsiveness suggests that neonatal dexamethasone exposure permanently alters central nervous system function, particularly within the neuroendocrine stress axis. This may lead to increased risk for learning impairment and maladaptive responses to the environment.