TY - JOUR
T1 - Lipopolysaccharide preconditioning reduces neuroinflammation against hypoxic ischemia and provides long-term outcome of neuroprotection in neonatal rat
AU - Lin, Hsiang Yin
AU - Huang, Chao Ching
AU - Chang, Kang Fan
PY - 2009/9
Y1 - 2009/9
N2 - Hypoxic ischemia (HI) in newborns causes long-term neurologic abnormalities. Systemic lipopolysacchari.de (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 macro-phage 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.
AB - Hypoxic ischemia (HI) in newborns causes long-term neurologic abnormalities. Systemic lipopolysacchari.de (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 macro-phage 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.
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U2 - 10.1203/PDR.0b013e3181b0d336
DO - 10.1203/PDR.0b013e3181b0d336
M3 - Article
C2 - 19531979
AN - SCOPUS:70350450344
SN - 0031-3998
VL - 66
SP - 254
EP - 259
JO - Pediatric Research
JF - Pediatric Research
IS - 3
ER -