Lipopolysaccharide preconditioning reduces neuroinflammation against hypoxic ischemia and provides long-term outcome of neuroprotection in neonatal rat

Pediatr Res. 2009 Sep;66(3):254-9. doi: 10.1203/PDR.0b013e3181b0d336.


Hypoxic ischemia (HI) in newborns causes long-term neurologic abnormalities. Systemic lipopolysaccharide (LPS) is neuroprotective in neonatal rats when injected 24 h 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 h before HI greatly increased microglial cell and macrophage activation and up-regulated TNF-alpha and inducible NOS expression 12-h postinjection 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 inducible NOS expression and resulted in low mortality. Given 24 h before HI, low-dose (0.05 mg/kg) LPS greatly reduced microglia and macrophage activation, TNF-alpha expression, and reactive oxygen species production 24-h 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 among 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 pathologic abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects
  • Brain* / drug effects
  • Brain* / metabolism
  • Brain* / pathology
  • CD11b Antigen / metabolism
  • Female
  • Hypoxia-Ischemia, Brain* / metabolism
  • Hypoxia-Ischemia, Brain* / pathology
  • Ischemic Preconditioning / methods*
  • Lipopolysaccharides / metabolism*
  • Neuroprotective Agents / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • CD11b Antigen
  • Lipopolysaccharides
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II