EFFECT OF ADVERSE PERINATAL EXPERIENCES ON CORTICAL ORGANIZATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 与早产相关的不良经历与早产儿童的认知和行为缺陷有关，这表明大脑皮质--参与智力和智力的主要大脑区域--受到了破坏。然而，还没有确定早产儿会经历疼痛或疼痛引起的神经后果，也不知道麻醉药在这个年龄段的好处是否大于坏处。这个项目的总体目标是了解新生儿疼痛和/或麻醉是如何影响大脑结构发育、成熟和衰老的方式，重点是皮质，以及参与正常皮质发育的一组细胞-亚板神经元的作用。我们假设，当围产期哺乳动物暴露在反复疼痛或长期麻醉下时，皮质组织会发生不可挽回的变化，如果给药一段适当的时间，这种破坏可以降到最低。由于暴露在反复新生儿疼痛和/或麻醉下的大鼠会出现类似于早产儿的缺陷，我们建议对使用和不使用麻醉药的啮齿动物的皮质进行表征。利用细胞标记技术，以及相关的光和荧光显微镜，我们将比较处理组和对照组动物在发育过程中皮质的结构，包括亚板神经元。利用生物信息学技术，我们将在实验动物中产生合适的麻醉间隔的预测。使用这些数据，我们将开始了解皮质破坏如何与早产儿相关的发育障碍有关。预计这项研究将向学生展示生物医学研究职业的潜力，并支持联邦政府为本科生的研究经验提供资金，并最终导致制定联邦资金提案，继续详细调查大脑皮质功能障碍在发育障碍中的表现。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The adverse experiences related to preterm birth are associated with cognitive and behavioral defects in ex-preterm children, indicating disruption of the cortex, the primary brain region involved in aptitude and intelligence. Nevertheless, it has not been established that premature infants experience pain or neural consequences from pain, nor is it known if the benefits of anesthetic drugs outweigh disadvantages in this age group. The overall goals of this project are to understand how pain and/or anesthesia in newborns affects the manner in which brain architecture develops, matures, and ages, with a focus on the cortex, and the role of group of a cells critically involved in normal cortical development, the subplate neurons. We hypothesize that when perinatal mammals are exposed to repetitive pain or prolonged anesthesia, cortical organization is irreparably altered, a disruption that can be minimized if anesthesia is administered for an appropriate time period. Because rats exposed to repetitive neonatal pain and/or anesthesia develop deficits mimicking those of ex-preterm children, we propose to characterize the cortex of rodents that have undergone adverse perinatal experiences with and without anesthetic drugs. Utilizing cellular labeling techniques, and correlated light and fluorescent microscopy, we will compare the structure of the cortex, including subplate neurons, between treated and control animals across development. Using bioinfomatic techniques, we will generate predictions for appropriate anesthetic intervals in experimental animals. Using these data, we will begin to understand how cortical disruption may be implicated in developmental disorders associated with ex-preterm children. It is expected that this research will demonstrate to students the potential of careers in biomedical research, as well as support federal funding for undergraduate research experiences, and ultimately lead to the development of proposals for federal funds to continue to investigate in detail how disruption of the cortex may be evidenced in developmental disorders.