OPTIMIZING NEUROPROTECTION FOLLOWING PERINATAL ASPHYXIA

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 围产期窒息，定义为分娩期间胎儿严重缺氧，仍然是一个严重的健康问题，占全球新生儿死亡的23%。高达60%的幸存者患有严重的终身神经发育障碍，包括智力低下、脑瘫、癫痫发作和学习障碍。这项研究的目标是开发一种治疗围产期窒息的方法，以减少因大脑缺氧而造成的神经损伤，从而帮助受影响的儿童充分发挥潜力，过上健康和富有成效的生活。在新生和成年动物模型中，促红细胞生成素(EPO)和亚低温都具有神经保护作用，可以改善脑损伤后的短期和长期神经预后。这两种治疗方法都不能完全起到保护作用。我们假设EPO联合低温治疗比单独使用任何一种治疗方法都能更好地减少围产期窒息的后遗症。我们已经建立了一个围产期窒息的模型，它能够在非常类似于人类新生儿紧急情况的条件下测试联合神经保护治疗策略的有效性和安全性。我们将使用这个模型来测试以下具体目标：1)比较EPO或单独使用EPO、EPO联合低温和安慰剂对中度围产期窒息的神经发育和结构后遗症的疗效；2)测试这些治疗的个体和联合安全性。评估将包括EEG、MRI、神经行为评估、生化和免疫组织化学研究。这项工作将产生直接临床应用的重要数据，旨在大幅减少出生窒息造成的经济和情感后果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Perinatal asphyxia, defined as a severe lack of oxygen to the fetus during labor and delivery, remains a significant health problem, accounting for 23% of neonatal deaths worldwide. Up to 60% of survivors are left with severe and life-long neurodevelopmental handicaps that include mental retardation, cerebral palsy, seizures and learning disabilities. The goal of this research is to develop an approach to perinatal asphyxia that will decrease the neurologic injury sustained from lack of oxygen to the brain, thereby helping affected children achieve their full potential and lead healthy and productive lives. Both erythropoietin (Epo) and hypothermia are neuroprotective, improving short and long term neurologic outcome following brain injury in neonatal and adult animal models. Neither treatment is completely protective. We hypothesize that Epo combined with hypothermia will decrease the sequelae of perinatal asphyxia more than either therapy alone. We have established a model of perinatal asphyxia which enables testing of the efficacy and safety of a combined neuroprotective treatment strategy under conditions that closely resemble human neonatal emergencies. We will use this model to test the following specific aims: 1) to compare the efficacy of Epo or hypothermia alone, Epo with hypothermia, and placebo on the neurodevelopmental and structural sequelae of moderate perinatal asphyxia; 2) to test the individual and combined safety of these treatments. Evaluation will include EEG, MRI, neurobehavioral evaluations, biochemical and immunohistochemical studies. This work will produce important data with direct clinical application directed towards substantially lessening the financial and emotional consequences of birth asphyxia.