Lipopolysaccharide Preconditioning Reduces Neuroinflammation against Hypoxic Ischemia and Provides Long-Term Outcome of Neuroprotection in Neonatal Rat.
Hypoxic ischemia (HI) in newborns causes long-term neurological abnormalities. Systemic lipopolysaccharide (LPS) is neuroprotective in neonatal rats when injected 24 hours before HI. However, the effect on HI-induced neuroinflammation and the long-term outcome of LPS preconditioning in neonatal rats have not been examined. In a rat-pup HI model, compared with normal saline (NS), 0.3 mg/kg of LPS injected 24 hours before HI greatly increased microglial cell and macrophage activation and upregulated TNF-alpha and iNOS expression 12 hours post-injection, and resulted in high mortality during HI. In contrast, 0.05 mg/kg of LPS elicited very little microglia and macrophage activation and TNF-alpha and iNOS expression, and resulted in low mortality. Given 24 hours before HI, low-dose (0.05 mg/kg) LPS greatly reduced microglia and macrophage activation, TNF-alpha expression, and reactive oxygen species production 24 hours post-HI compared with NS-treated rats. Rats in the low-dose LPS group also showed significantly better learning and memory and less brain damage in adulthood. Learning and memory performance between the LPS-HI, LPS, and NS groups was not significantly different. We conclude that low-dose LPS preconditioning in neonatal rats greatly reduces HI-induced neuroinflammation, and provides long-term neuroprotection against behavioral and pathological abnormalities.
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