Intrauterine infection induces programmed cell death in rabbit periventricular white matter

被引:101
作者
Debillon, T
Gras-Leguen, C
Vérielle, V
Winer, N
Caillon, J
Rozé, JC
Gressens, P
机构
[1] Hop Mere Enfant, Dept Perinatol, F-44093 Nantes 1, France
[2] Univ Med, Lab Antibiol, F-44093 Nantes, France
[3] Ctr Paul Papin, Lab Anatomopathol, F-49033 Angers 1, France
[4] Hop Robert Debre, Serv Neurol Pediat, F-75019 Paris, France
[5] Hop Robert Debre, INSERM, E9935, F-75019 Paris, France
关键词
D O I
10.1203/00006450-200006000-00009
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
An association between chorioamnionitis and periventricular leukomalacia has been reported in human preterm infants. However, whether this link is causal has not been convincingly established, and the underlying molecular mechanisms remain unclear. The objective of this study was to establish a reproducible model of cerebral white matter disease in preterm rabbits after intrauterine infection. Escherichia coli was inoculated into both uterine horns of laparotomized pregnant rabbits when gestation was 80% complete. The fetuses were delivered by cesarean section and killed 12, 24, or 48 h after the inoculation. Programmed cell death in the white matter was evaluated by hematoxylin-eosin-saffron staining and in situ fragmented DNA labeling (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). In a first group of 14 pregnant rabbits not treated with antibiotics, all fetuses delivered 48 h after inoculation were stillborn, whereas fetuses extracted 12 or 24 h after inoculation were alive. No significant cell death was detected in the live fetuses compared with the control noninfected rabbits. In a second group of five pregnant rabbits treated with ceftriaxone initiated 24 h after the inoculation and continued until cesarean section was performed 48 h after inoculation, 13 fetuses were alive, but all showed evidence of extensive programmed cell death in the white matter by hematoxylin-eosin-saffron staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. White matter damage became histologically detectable only 48 h after inoculation. Three of the 13 brains displayed periventricular white matter cysts mimicking human cystic periventricular leukomalacia. The high reproducibility of white matter damage in our model should permit further studies aimed at unraveling the molecular mechanisms of periventricular leukomalacia.
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页码:736 / 742
页数:7
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