EFFECT OF ADVERSE PERINATAL EXPERIENCES ON CORTICAL ORGANIZATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。与早产有关的不良经历与早产前儿童的认知和行为缺陷有关，表明大脑皮层（涉及天资和智力的主要大脑区域）受到破坏。然而，尚未确定早产儿是否会经历疼痛或疼痛引起的神经后果，也不知道麻醉药物对这个年龄组的好处是否大于坏处。该项目的总体目标是了解新生儿的疼痛和/或麻醉如何影响大脑结构的发育、成熟和衰老，重点关注皮层，以及一组在正常皮层发育中至关重要的细胞——底板神经元的作用。我们假设，当围产期哺乳动物暴露于重复性疼痛或长时间麻醉时，皮质组织会发生不可修复的改变，如果麻醉时间适当，这种破坏可以最小化。由于暴露于重复性新生儿疼痛和/或麻醉的大鼠会出现模仿早产儿的缺陷，我们建议对经历过有或没有麻醉药物的不良围产期经历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，我们将比较处理和对照动物在整个发育过程中的皮层结构，包括亚板神经元。利用生物信息学技术，我们将对实验动物的适当麻醉间隔进行预测。利用这些数据，我们将开始了解皮质破坏如何与前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的职业潜力，并支持联邦资助本科生的研究经历，并最终导致联邦基金的发展，以继续详细调查大脑皮层的破坏如何在发育障碍中得到证明

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 disord