Pretreatment with Human Chorionic Gonadotropin Protects the Neonatal Brain against the Effects of Hypoxic-Ischemic Injury.
Pretreatment with Human Chorionic Gonadotropin Protects the Neonatal Brain against the Effects of Hypoxic-Ischemic Injury.
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DOI：
10.3389/fped.2017.00232
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发表时间：
2017
影响因子：
2.6
通讯作者：
Galindo R
中科院分区：
文献类型：
--
作者：
Movsas TZ;Weiner RL;Greenberg MB;Holtzman DM;Galindo R
虽然人类胎儿在整个妊娠期间都暴露在胎盘来源的人绒毛膜促性腺激素(HCG)中，但hCG对胎儿大脑的作用尚不清楚。对现有文献的回顾似乎表明，怀孕期间hCG平均水平较高的妇女组，其后代往往具有较低的脑性瘫痪(CP)风险。鉴于新生儿脑损伤往往先于脑性瘫痪的发展，我们的目的是确定hCG是否可以预防新生儿脑损伤的神经退行性变化。采用新生7日龄小鼠脑缺氧缺血(HI)模型，观察在HI前15~18 h、HI后1 h或HI后即刻给予hCG是否能减少损伤后7 d的脑组织丢失。接下来，我们通过将未成熟的大脑皮层和海马神经元暴露于hCG，并检测谷氨酸受体介导的兴奋性毒性损伤前后轴突的萌发和神经元存活，来研究hCG在神经元中是否具有促存活和营养特性。结果发现，在HI前15 h腹腔注射hCG，而不是在HI诱导后1 h注射hCG，可显著减少脑损伤后7 d的海马区和纹状体组织的丢失。此外，当神经元持续暴露于N-甲基-D-天冬氨酸10 天或给予该激素时及神经元损伤后，hCG在体外可降低N-甲基-D-天冬氨酸介导的神经元兴奋毒性。此外，体外连续给予人绒毛膜促性腺激素6-9 可增加轴突萌发和基础神经元存活率，MAP2免疫反应性至少增加1倍，NeuN + 免疫反应性增加2.5倍。我们的研究结果表明，hCG可以减轻HI相关的未成熟神经退行性变。其作用机制可能部分与抑制NMDA依赖的兴奋性毒性损伤有关。这项研究支持这样一种假设，即孕期hCG有可能保护发育中的大脑免受HI的影响，HI是CP的一个重要危险因素。
Though the human fetus is exposed to placentally derived human chorionic gonadotropin (hCG) throughout gestation, the role of hCG on the fetal brain is unknown. Review of the available literature appears to indicate that groups of women with higher mean levels of hCG during pregnancy tend to have offspring with lower cerebral palsy (CP) risk. Given that newborn cerebral injury often precedes the development of CP, we aimed to determine whether hCG may protect against the neurodegenerative effects of neonatal brain injury. We utilized the Rice–Vannucci model of neonatal cerebral hypoxia-ischemia (HI) in postnatal day 7 mice to examine whether intraperitoneal administration of hCG 15–18 h prior, 1 h after or immediately following HI decrease brain tissue loss 7 days after injury. We next studied whether hCG has pro-survival and trophic properties in neurons by exposing immature cortical and hippocampal neurons to hCG in vitro and examining neurite sprouting and neuronal survival prior and after glutamate receptor-mediated excitotoxic injury. We found that intraperitoneal injection of hCG 15 h prior to HI, but not at or 1 h after HI induction, resulted in a significant decrease in hippocampal and striatal tissue loss 7 days following brain injury. Furthermore, hCG reduced N-methyl-d-aspartate (NMDA)-mediated neuronal excitotoxicity in vitro when neurons were continuously exposed to this hormone for 10 days or when given at the time and following neuronal injury. In addition, continuous in vitro administration of hCG for 6–9 days increased neurite sprouting and basal neuronal survival as assessed by at least a 1-fold increase in MAP2 immunoreactivity and a 2.5-fold increase in NeuN + immunoreactivity. Our findings suggest that hCG can decrease HI-associated immature neural degeneration. The mechanism of action for this neuroprotective effect may partly involve inhibition of NMDA-dependent excitotoxic injury. This study supports the hypothesis that hCG during pregnancy has the potential for protecting the developing brain against HI, an important CP risk factor.
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影响因子：
7.5
作者：
Gallego MJ;Porayette P;Kaltcheva MM;Bowen RL;Vadakkadath Meethal S;Atwood CS
通讯作者：
Atwood CS
DOI：
10.1002/tera.1420370403
发表时间：
1988-04-01
期刊：
TERATOLOGY
影响因子：
--
作者：
DEPUE, RH
通讯作者：
DEPUE, RH
影响因子：
3.6
作者：
AlHader, AA;Lei, ZM;Rao, CV
通讯作者：
Rao, CV
影响因子：
3
作者：
BARTELS, I;HOPPESIEVERT, B;CAESAR, J
通讯作者：
CAESAR, J
影响因子：
2.4
作者：
Gol, M;Altunyurt, S;Demir, N
通讯作者：
Demir, N