Intrauterine administration of endotoxin leads to motor deficits in a rabbit model: a link between prenatal infection and cerebral palsy

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• 作者：Fadoua Saadani-Makki ; Sujatha Kannan ; Xin Lu ; James Janisse ; Elizabeth Dawe ; Samuel Edwin ; Roberto Romero ; Diane Chugani
• 关键词：cerebral palsy ; intrauterine inflammation ; microglia ; perinatal brain injury
• 刊名：American Journal of Obstetrics and Gynecology
• 出版年：2008
• 出版时间：December 2008
• 年：2008
• 卷：199
• 期：6
• 页码：651.e1-651.e7
• 全文大小：508 K

文摘

Objective

This study was undertaken to determine whether maternal intrauterine endotoxin administration leads to neurobehavioral deficits in newborn rabbits.

Study Design

Pregnant New Zealand white rabbits were injected with 1 mL saline solution (n = 8) or 20 μg/kg of lipopolysaccharide in saline solution (n = 8) into the uterine wall on day 28/31 of gestation. On postnatal day 1, kits (saline solution [n = 30] and lipolysaccharide in saline solution [n = 18] from 4 consecutive litters) underwent neurobehavioral testing. Neonatal brains were stained for microglial cells and myelin.

Results

Kits in the lipopolysaccharide in saline solution group were hypertonic and demonstrated significant impairment in posture, righting reflex, locomotion, and feeding, along with neuroinflammation indicated by activated microglia and hypomyelination in the periventricular regions. A greater mortality was noted in the lipopolysaccharide in saline solution group (16 stillbirths from 3 litters vs 3 from 1 litter).

Conclusion

Maternal intrauterine endotoxin administration leads to white matter injury and motor deficits in the newborn rabbit, resulting in a phenotype that resembles those found in periventricular leukomalacia and cerebral palsy.