Abstract: Objective To explore the effect of low-concentration lipopolysaccharide (LPS) pretreatment on hyperoxia-induced
immature brain injury in neonatal mice and explore and the related mechanisms. Methods Forty-eight neonatal mice on
postnatal day 3 (PND3) were randomized into normal control group, LPS (0.3 mg/kg) group, hyperoxia group (hyperoxia
exposure for 24 h), and hyperoxia+LPS group (hyperoxia exposure for 24 h 30 min after 0.3 mg/kg LPS treatment). At PND5,
all the neonatal mice were sacrificed to examine the morphological changes of microglia in the periventricular white matter
using Tomato lectin staining, measure malondialdehyde (MDA) content in the immature brain, detect mRNA expression of
tumor necrosis factor-α (TNF-α) using real-time PCR, and determine caspase-3 protein expression with Western blotting.
Results Compared with the control group, exposures to LPS, hyperoxia, and both all resulted in microglia activation in the
periventricular white matter. The number of activated microglia, MDA content, TNF-α mRNA expression and caspase-3
protein expression in the immature brain were significantly higher in hyperoxia group than in the control group and LPS
group (P<0.05). LPS pretreatment significantly enhanced hyperoxia-induced microglia activation in the immature brain (P<
0.05). Conclusion Hyperoxia causes immature brain injury mediated by microglia activation, and LPS pretreatment can
enhance such brain injury in neonatal mice.