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 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.
Lin
Hsiang-Yin
HY
Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan City 70428, Taiwan.
Huang
Chao-Ching
CC
Chang
Kang-Fan
KF
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008070:Lipopolysaccharides / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D039481:CD11b Antigen; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II