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

Fadoua Saadani-Makki, Sujatha Kannan, Xin Lu, James Janisse, Elizabeth Dawe, Samuel Edwin, Roberto Romero, Diane Chugani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)651.e1-651.e7
JournalAmerican journal of obstetrics and gynecology
Volume199
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

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Keywords

  • cerebral palsy
  • intrauterine inflammation
  • microglia
  • perinatal brain injury

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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