OPTIMIZING NEUROPROTECTION FOLLOWING PERINATAL ASPHYXIA

优化围产期窒息后的神经保护

基本信息

批准号：
8172774
负责人：
Sandra E Juul
金额：
$ 15.51万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2011-04-30
项目状态：
已结题

项目摘要

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. Perinatal asphyxia accounts for 23% of neonatal deaths globally. Up to 60% of survivors are left with life-long neurodevelopmental handicaps that include mental retardation, cerebral palsy, seizures and learning disabilities. Effective treatment strategies are currently limited: Hypothermia has been shown to decrease brain injury, but only for mild and moderate asphyxia; recombinant erythropoietin (rEpo) improves both short and long term neurologic outcome following brain injury in animal models, but has not been tested in human infants. Neither treatment provides complete protection. Our goal is to develop a safe and effective treatment for perinatal asphyxia that will decrease the subsequent neurologic injury, thereby helping affected children achieve their full potential and lead healthy and productive lives. We hypothesize that both rEpo and hypothermia will decrease the neurodevelopmental and structural consequences of perinatal asphyxia in near-term pigtailed macaques (Macaca nemestrina), and that combined therapy with rEpo and hypothermia will provide even greater benefit. We will utilize a non-human primate model of perinatal asphyxia to test the following specific aims: Aim 1) To determine which therapeutic strategy is most effective in decreasing the neurodevelopmental sequelae of perinatal asphyxia in near-term M. nemestrina: rEpo alone, hypothermia alone, or rEpo plus hypothermia (vs. vehicle controls); Aim 2) To determine which therapeutic strategy is most effective in decreasing the structural consequences of perinatal asphyxia in brains of near-term M. nemestrina: rEpo alone, hypothermia alone, or rEpo plus hypothermia (vs. vehicle controls); Aim 3) To establish the safety of high dose rEpo treatment, hypothermia, and rEpo plus hypothermia in near-term M. nemestrina exposed to perinatal asphyxia. This work will produce important data with direct clinical application to perinatal asphyxia, and possibly to other mechanisms of brain injury in infants and children.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。围产期窒息占全球新生儿死亡的23％。多达60％的幸存者留下了终生的神经发育障碍，包括智力低下，脑瘫，癫痫发作和学习障碍。目前有效的治疗策略受到限制：体温过低已显示可减少脑损伤，但仅针对轻度和中度的窒息；重组红细胞生成素（repo）在动物模型中脑损伤后改善了短期和长期神经系统损伤，但尚未在人类婴儿中进行测试。两项治疗都没有提供完整的保护。我们的目标是为围产期窒息开发一种安全有效的治疗方法，以减少随后的神经系统损伤，从而帮助受影响的儿童发挥其全部潜力并带来健康和富有生产力的生活。我们假设回购和体温过低都会降低近期尾巴猕猴（Macaca nemestrina）中围产期窒息的神经发育和结构性后果，而这种与repo和repo和低温的疗法将提供更大的好处。 We will utilize a non-human primate model of perinatal asphyxia to test the following specific aims: Aim 1) To determine which therapeutic strategy is most effective in decreasing the neurodevelopmental sequelae of perinatal asphyxia in near-term M. nemestrina: rEpo alone, hypothermia alone, or rEpo plus hypothermia (vs. vehicle controls);目的2）确定哪种治疗策略最有效地减少了近期Nemestrina的大脑中围产期窒息的结构后果：单独的回购，单独的低温或回购加上低温（与车辆控制）；目标3）在接触围产期窒息的近期尼梅斯特菌中，建立高剂量回购治疗，体温过低和回购和体温过低的安全性。这项工作将产生重要的数据，并直接临床应用于围产期窒息，并可能针对婴儿和儿童的其他脑损伤机制。