Summary： Activated protein C （APC）, a natural anticoagulant, has been reported to exert direct vascu- loprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. ...Summary： Activated protein C （APC）, a natural anticoagulant, has been reported to exert direct vascu- loprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. In- traperitoneal injection of 300 ~tg/kg lipopolysaccharide （LPS） was administered consecutively to preg- nant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infec- tion-induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats imme- diately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eo- sin （H＆E）. Immunohistochemistry was used to evaluate myelin basic protein （MBP） expression in the periventricular white matter region. Blood-brain barrier （BBB） permeability and brain water content ~were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 （PAR1）. Typical pathological changes of white matter injury were ob- served in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely acti- vated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein ex- pression levels were both down-regulated. Our results suggested that APC exerted neuroprotective ef- fects on multiple components of the neurovascular unit in neonatal rats with intrauterine infec- tion-induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.展开更多
目的总结先天性膈疝(congenital diaphragmatic hernia, CDH)产前程序化管理的临床结局。方法收集产前诊断为左侧膈疝患儿,回顾分析在产前程序化管理下CDH的新生儿期临床结局。结果左侧胎儿膈疝共计39例。4例(10.3%)胎儿膈疝终止妊娠(T...目的总结先天性膈疝(congenital diaphragmatic hernia, CDH)产前程序化管理的临床结局。方法收集产前诊断为左侧膈疝患儿,回顾分析在产前程序化管理下CDH的新生儿期临床结局。结果左侧胎儿膈疝共计39例。4例(10.3%)胎儿膈疝终止妊娠(TOP)。1例TOP患儿产前超声和MRI评估为中重度并染色体异常,另外3例未做产前严重程度分级。在出生的病例中,产前超声或MRI评估为中重度者17例,轻度者19例。CDH新生儿期病死率为15.4%(6/39)(均产前评估为中重度者)。在分娩的中重度CDH患儿中,新生儿期病死率为26.7%(4/15),体外膜肺氧合(ECMO)使用率为26.7%(4/15)。50%(2/4)的ECMO患儿在新生儿期存活。与轻度膈疝患儿相比,中重度膈疝患儿的补片使用比例更高(60.0%vs.25.0%,P<0.05),住院的中位时间[34.0(15.9,63.7) d vs. 16.0(12.5,21.3) d,P<0.05]及机械通气的中位时间更长[14.0(7.6,22.2) d vs. 3.5(2.7,7.3) d,P<0.05)。结论产前程序化管理对于胎儿CDH的救治具有必要性和重要性,新生儿期临床结局满意。展开更多
基金supported by grants from National Natural Science Foundation of China(No.81471519 and No.81401277)the Program for Changjiang Scholars and Innovative Research Team in University of China(No.IRT_14R20)
文摘Summary： Activated protein C （APC）, a natural anticoagulant, has been reported to exert direct vascu- loprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. In- traperitoneal injection of 300 ~tg/kg lipopolysaccharide （LPS） was administered consecutively to preg- nant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infec- tion-induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats imme- diately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eo- sin （H＆E）. Immunohistochemistry was used to evaluate myelin basic protein （MBP） expression in the periventricular white matter region. Blood-brain barrier （BBB） permeability and brain water content ~were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 （PAR1）. Typical pathological changes of white matter injury were ob- served in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely acti- vated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein ex- pression levels were both down-regulated. Our results suggested that APC exerted neuroprotective ef- fects on multiple components of the neurovascular unit in neonatal rats with intrauterine infec- tion-induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.
文摘目的总结先天性膈疝(congenital diaphragmatic hernia, CDH)产前程序化管理的临床结局。方法收集产前诊断为左侧膈疝患儿,回顾分析在产前程序化管理下CDH的新生儿期临床结局。结果左侧胎儿膈疝共计39例。4例(10.3%)胎儿膈疝终止妊娠(TOP)。1例TOP患儿产前超声和MRI评估为中重度并染色体异常,另外3例未做产前严重程度分级。在出生的病例中,产前超声或MRI评估为中重度者17例,轻度者19例。CDH新生儿期病死率为15.4%(6/39)(均产前评估为中重度者)。在分娩的中重度CDH患儿中,新生儿期病死率为26.7%(4/15),体外膜肺氧合(ECMO)使用率为26.7%(4/15)。50%(2/4)的ECMO患儿在新生儿期存活。与轻度膈疝患儿相比,中重度膈疝患儿的补片使用比例更高(60.0%vs.25.0%,P<0.05),住院的中位时间[34.0(15.9,63.7) d vs. 16.0(12.5,21.3) d,P<0.05]及机械通气的中位时间更长[14.0(7.6,22.2) d vs. 3.5(2.7,7.3) d,P<0.05)。结论产前程序化管理对于胎儿CDH的救治具有必要性和重要性,新生儿期临床结局满意。
