Research ReportLipopolysaccharide-preconditioning protects against endotoxin-induced white matter injury in the neonatal rat brain

BackgroundExposing 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) 500 μg/kg LPS administrated i.p. on days 18 and 19 (PVL group), (iii) 50 μg/kg LPS administrated i.p. on day 17 followed by 500 μg/kg LPS i.p. on days 18 and 19 (PC-PVL group), (iv) 50 μg/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 24 h 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. Conclusion: 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.

► Early endotoxin exposure leads periventricular white matter injury in the immature rat brain. ► LPS pretreatment (preconditioning) protected the immature brain from subsequent endotoxic damage. ► Induction of brain Superoxide dismutase activity contributed to LPS induced preconditioning. ► Reduced expression of tumor necrotizing factor-alpha contributed to LPS induced-preconditioning.