Lipopolysaccharide-preconditioning protects against endotoxin-induced white matter injury in the neonatal rat brain.
BACKGROUND
Exposing the brain to a sub-damaging stimulus can protect against a subsequent lethal insult, a phenomenon termed preconditioning. The aim of this study was to investigate the neuroprotective effect of low dose LPS (lipopolysaccharide) pretreatment in endotoxin induced periventricular leukomalacia (PVL) in a rat model.


METHODS
Wistar rats with dated pregnancies were allocated to 5 groups: (i) no LPS administered, intraperitoneally (i.p.) pyrogen-free saline injected (Control group), (ii) 500μg/kg LPS administrated i.p. on days 18 and 19 (PVL group), (iii) 50μg/kg LPS administrated i.p. on day 17 followed by 500μg/kg LPS i.p. on days 18 and 19 (PC-PVL group), (iv) 50μg/kg LPS administrated on day 17 (PC only), and (v) i.p. pyrogen-free saline injected control group on day 17.


RESULTS
LPS-preconditioning given 24h before potent LPS exposure significantly reduced the number of apoptotic cell deaths and prevented hypomyelination. Antioxidant enzyme gene expression levels (Superoxide Dismutase-SOD1, SOD2, and SOD3) were increased and Tumor Necrosis Factor (TNF)α expression levels were decreased in the PC+PVL group when compared with the PVL group.


CONCLUSIONS
Low-dose LPS given one day before potent doses of LPS reduces antepartum LPS-induced brain damage. The mechanisms of protection might involve oxidation and inflammation.
Faculty of Medicine, Department of Pediatrics, School of Medicine, Inciratti, Dokuz Eylul University, Izmir 35340, Turkey.
Abdullah
A
Kumral
Funda
F
Tuzun
Seda
S
Ozbal
Bekir
B
Ugur Ergur
Osman
O
Yılmaz
Nuray
N
Duman
Hasan
H
Ozkan
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D056784:Leukoencephalopathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007969:Leukomalacia, Periventricular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; C499089:Sod3 protein, rat