Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth
Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth
复制标题
DOI：
10.1203/01.pdr.0000191141.21932.b6
复制
发表时间：
2006-01-01
影响因子：
3.6
通讯作者：
Sammel, MD
中科院分区：
文献类型：
--
作者：
Elovitz, MA;Mrinalini, C;Sammel, MD
不良的神经功能结局，包括脑瘫，是早产儿长期发病的重要因素。然而，在早产的情况下导致脑损伤的机制知之甚少。在过去的十年中，越来越多的证据表明感染或炎症与早产有关。宫内炎症的存在显著增加了新生儿神经系统不良结局的风险。进行这些研究以阐明可能导致长期神经损伤的胎脑中激活的早期信号转导通路。使用我们的小鼠模型，局部子宫内炎症，TH 1/TH 2途径的激活在胎盘，胎体，胎肝，胎脑进行了研究。进一步的研究确定了TH 1/TH 2通路的激活是否会促进细胞死亡并改变神经胶质细胞的发育。实时PCR研究表明，一个强大的TH 1/TH 2反应迅速发生在胎儿大脑暴露于宫内炎症后。胎儿和胎盘中的细胞因子反应与胎儿脑中的反应无显著相关性。沿着免疫应答，细胞死亡途径在胎儿脑中响应于宫内LPS而被早期激活。我们发现GFAP mRNA和蛋白质的增加以及前少突胶质细胞的丢失暗示了TH 1/TH 2和细胞死亡途径在永久性脑损伤中的作用。随着对炎症促进早产儿脑损伤的机制的了解的增加，确定潜在的靶点以限制不良新生儿结局成为可能。
Adverse neurologic outcome, including cerebral palsy, is a significant contributor to long-term morbidity in preterm neonates. However, the mechanisms leading to brain injury in the setting of a preterm birth are poorly understood. In the last decade, there has been a growing body of evidence correlating infection or inflammation with preterm birth. The presence of intrauterine inflammation significantly increases the risk for adverse neurologic Outcome in the neonate. These studies were performed to elucidate the early signal transduction pathways activated in the fetal brain that may result in long-term neurologic injury. Using our mouse model of localized intrauterine inflammation, the activation of TH1/TH2 pathways in the placenta, fetus corpus, fetal liver, and fetal brain was investigated. Additional studies determined whether activation of TH1/TH2 pathways could promote cell death and alter glial development. Real-time PCR studies demonstrated that a robust TH1/TH2 response occurs rapidly in the fetal brain after exposure to intrauterine inflammation. The cytokine response in the fetus and placenta was not significantly correlated with the response in the fetal brain. Along with an immune response, cell death pathways were activated early in the fetal brain in response to intrauterine LPS. Implicating TH1/TH2 and cell death pathways in permanent brain injury are our findings of an increase in GFAP mRNA and protein as well as a loss of pro-oligodendrocytes. With increased understanding of the mechanisms by which inflammation promotes brain injury in the preterm neonate, identification of potential targets to limit adverse neonatal outcomes becomes possible.