Intracisternal application of endotoxin enhances the susceptibility to subsequent hypoxic-ischemic brain damage in neonatal rats.
Perinatal brain damage is associated not only with hypoxic-ischemic insults but also with intrauterine inflammation. A combination of antenatal inflammation and asphyxia increases the risk of cerebral palsy >70 times. The aim of the present study was to determine the effect of intracisternal (i.c.) administration of endotoxin [lipopolysaccharides (LPS)] on subsequent hypoxic-ischemic brain damage in neonatal rats. Seven-day-old Wistar rats were subjected to i.c. application of NaCl or LPS (5 microg/pup). One hour later, the left common carotid artery was exposed through a midline neck incision and ligated with 6-0 surgical silk. After another hour of recovery, the pups were subjected to a hypoxic gas mixture (8% oxygen/92% nitrogen) for 60 min. The animals were randomized to four experimental groups: 1) sham control group, left common carotid artery exposed but not ligated (n = 5); 2) LPS group, subjected to i.c. application of LPS (n = 7); 3) hypoxic-ischemic study group, i.c. injection of NaCl and exposure to hypoxia after ligation of the left carotid artery (n = 17); or 4) hypoxic-ischemic/LPS study group, i.c. injection of LPS and exposure to hypoxia after ligation of the left carotid artery (n = 19). Seven days later, neonatal brains were assessed for neuronal cell damage. In a second set of experiments, rat pups received an i.c. injection of LPS (5 microg/pup) and were evaluated for tumor necrosis factor-alpha expression by immunohistochemistry. Neuronal cell damage could not be observed in the sham control or in the LPS group. In the hypoxic-ischemic/LPS group, neuronal injury in the cerebral cortex was significantly higher than in animals that were subjected to hypoxia/ischemia after i.c. application of NaCl. Injecting LPS intracisternally caused a marked expression of tumor necrosis factor-alpha in the leptomeninges. Applying LPS intracisternally sensitizes the immature rat brain to a subsequent hypoxic-ischemic insult.
Coumans
Audrey B C
AB
Department of Obstetrics and Gynecology, University Hospital Maastricht, The Netherlands.
Middelanis
Johannes S
JS
Garnier
Yves
Y
Vaihinger
Hans-Martin
HM
Leib
Stephen L
SL
Von Duering
Monika U
MU
Hasaart
Tom H M
TH
Jensen
Arne
A
Berger
Richard
R
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002946:Cisterna Magna; D004198:Disease Susceptibility; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides