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Novel Mechanisms of Neonatal Hypoxic-Ischemic Brain Injury and Repair

新生儿缺氧缺血性脑损伤及修复的新机制

基本信息

批准号：
7737057
负责人：
Wei-Hua Lee
金额：
$ 36.45万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7737057
关键词：
Acute Animal Model Apoptosis Authorization documentation Behavior Biological Process Biomedical Research Brain Brain Hypoxia-Ischemia Brain Injuries Budgets Cell Culture Techniques Cell Respiration Cessation of life Child Development Clinical Clinical Treatment Data Development Disease Doctor of Medicine Encephalopathies Ensure Equipment Experimental Designs Fibrinogen Funding Future Goals Hour Human Resources Hypoxia Immunohistochemistry In Vitro Indiana Individual Infant Infarction Injury Insulin-Like Growth Factor I Investigation Ischemic-Hypoxic Encephalopathy Knowledge Laboratories Microscope Modeling Neonatal Nervous system structure Neuronal Injury Neurons Newborn Infant Occupations Oligodendroglia Pathway interactions Patients Peer Review Perinatal Phase Postdoctoral Fellow Principal Investigator Proliferating Rattus Reagent Recovery Research Research Project Grants Research Training Role Scientist Sheep Site Somatomedins Study Section Survivors Testing Therapeutic Uses Time Training Treatment Efficacy Uncertainty Universities Work base cytokine disability effective therapy fetal immunocytochemistry improved in vivo in vivo Model injury and repair medical schools meetings neonatal hypoxic-ischemic brain injury neurogenesis neuron apoptosis novel outcome forecast prevent progenitor relating to nervous system repaired research study

项目摘要

Hypoxia-ischemia encephalopathy (HIE) remains a leading cause of severe brain damage that occurs in 0.1-0.2% of term or near-term infants, among whom approximately 20% die and up to 40% of the survivors often suffer devastating disabilities. To date, no effective clinical treatment is available to mitigate brain damage and improve the brain functional development of these children. Insulinlike growth factor I (IGF-I) is a pleiotrophic factor essential for the development of the mammalian nervous system. IGF-I reduced brain damage and improved the survival of hypoxic-ischemic rats and fetal sheep. Recently, we found that exogenous IGF-I was more effective in reducing hypoxic-ischemic brain injury and in improving functional behavior development,13 if given after 24 hours of recovery. We hypothesize that, in the delayed phase of hypoxia-ischemia recovery, IGF-I treatment will promote brain repair by (1) reducing delayed neuronal apoptosis; and (2) stimulating neuro- and oligodendrogenesis and revascularization. We will examine this novel hypothesis using complementary in vitro and in vivo models of hypoxia-ischemia. Aim 1 will characterize the mechanisms by which IGF-I prevents or reduces delayed neuronal apoptosis following hypoxia-ischemia. Aim 2 will investigate if and how IGF-I stimulates revascularization and neuro-/oligodendrogenesis following neonatal hypoxiaischemia. Results of this investigation will provide crucial information towards establishing an effective therapy for newborn patients suffering from hypoxicischemic encepholapathy.

缺氧缺血性脑病（Hypoxia-ischemia encephalopathy，HIE）是导致重症颅脑损伤的主要原因 0.1-0.2%的足月或近足月婴儿发生的损伤，其中大约20%的人死亡，多达40%的幸存者经常遭受毁灭性的痛苦，残疾。迄今为止，没有有效的临床治疗可用于减轻脑损伤。损害和促进这些孩子的大脑功能发育。胰岛素样生长因子I（IGF-I）是一种对发育至关重要的多营养因子，哺乳动物的神经系统IGF-I减少了脑损伤，缺氧缺血大鼠和胎羊的存活率。最近，我们发现，外源性IGF-I能更有效地减轻缺氧缺血性脑损伤在改善功能性行为发育方面，如果在24小时后给予，复苏我们推测，在缺氧缺血的延迟阶段，恢复，IGF-I治疗将促进脑修复（1）减少延迟神经元凋亡;和（2）刺激神经元和少突神经元发生，血运重建我们将使用互补的方法来检验这个新的假设。缺氧缺血的体外和体内模型。目标1将描述 IGF-I预防或减少迟发性神经元凋亡的机制缺氧缺血后。目标2将研究IGF-I是否以及如何刺激新生儿缺氧缺血后的血管重建和神经/少突神经发生。调查结果将提供重要信息，为新生儿缺氧缺血性疾病建立有效的治疗方法脑病