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Updated: May 2, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
[Lipopolysaccharide sensitizes neonatal mice to hyperoxia-induced immature brain injury]
1Department of Anesthesiology, Children's Hospital Affiliated to Chongqing Medical University/ Ministry of Education Key Laboratory of Child Development and Disorders/Key Laboratory of Pediatrics of Chongqing/Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China.E-mail: yang861104@163.com.
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.
