Intrauterine administration of endotoxin leads to motor deficits in a rabbit model: a link between prenatal infection and cerebral palsy.
OBJECTIVE
This study was undertaken to determine whether maternal intrauterine endotoxin administration leads to neurobehavioral deficits in newborn rabbits.


METHODS
Pregnant New Zealand white rabbits were injected with 1 mL saline solution (n = 8) or 20 microg/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).


CONCLUSIONS
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.
Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA.
Fadoua
F
Saadani-Makki
Sujatha
S
Kannan
Xin
X
Lu
James
J
Janisse
Elizabeth
E
Dawe
Samuel
S
Edwin
Roberto
R
Romero
Diane
D
Chugani
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001707:Biopsy, Needle; D002547:Cerebral Palsy / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004716:Endometritis / Q000139:chemically induced / Q000150:complications*; D004731:Endotoxins; D005260:Female; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D008070:Lipopolysaccharides; D009048:Motor Skills; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000139:chemically induced; D011270:Pregnancy, Animal; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D014599:Uterus / Q000187:drug effects
D004731:Endotoxins; D008070:Lipopolysaccharides