Antenatal bacterial endotoxin sensitizes the immature rat brain to postnatal excitotoxic injury.
Intracerebral injection of ibotenate in newborn rodents produces brain damage that mimics that of infants with cerebral palsy. Because maternal infection may contribute to brain injury in preterm infants, we investigated brain damage after maternal inflammation and postnatal ibotenate treatment in a rat model of cerebral palsy. Pregnant rats were injected intraperitoneally with lipopolysaccharide at Days 19 and 20 of gestation. Neonates were given intracerebral injections of ibotenate at postnatal Day 4 and were then killed at Day 9. Lesion sizes were measured by cresyl violet staining, and microglial activation, astrogliosis, and myelination were evaluated by immunohistochemistry. The lipopolysaccharide groups had larger cortical and white matter lesions than the control group; they also had significantly greater microglial activation and astrogliosis and less white matter myelination in the lesioned hemispheres compared with the controls. Thus, maternal endotoxin exposure may affect prenatal development of the offspring and modulate the subsequent development of excitotoxic brain lesions. These results demonstrate the critical influence of prenatal immune events on neonatal central nervous system vulnerability and provide a model for studying the pathophysiology of cerebral damage in preterm infants and, specifically, the interplay between brain inflammation and excitotoxicity.
Rousset
Catherine I
CI
INSERM U930, Université François Rabelais, and Neonatology Hôpital Clocheville, CHRU Tours, Tours, France.
Kassem
Jinane
J
Olivier
Paul
P
Chalon
Sylvie
S
Gressens
Pierre
P
Saliba
Elie
E
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D007051:Ibotenic Acid / Q000633:toxicity*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity*; D017628:Microglia / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000473:pathology; D009412:Nerve Fibers / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D039481:CD11b Antigen; D004731:Endotoxins; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D007051:Ibotenic Acid; C044101:endotoxin, Escherichia coli