Interaction Of Inflammation And Hyperoxia In A Mouse Model Of Neonatal White Matter Damage

Objective:To investigate the interaction of infection with systemic inflammation and normobaric hyperoxia in a mouse model of neonatal white matter damage.Methods:Three-day-old C57 BL /10 J mouse pups received 0.25mg/kg LPS i.p. and/or were subjected to 80% oxygen for 48 h, divided into air control(C) group, control+LPS group, hyperoxia(H) group, LPS+hyperoxia group. Those mice’s brain tissue were measured at P5,P12. Real-time PCR was applied to test the expression of IL-1β、TNF-α and NF-κB at mRNA level. The Concentration of the superoxide dismutase(SOD) of the brain homogenates was detected. The expression of Iba1 was detected by immunofluorescence assay to make sure the microglia type. Caspase3 activity and myelin basic protein(MBP) protein expression were determined by western-blot assay.Result:The mRNA expression of brain IL-1β、TNF-α and NF-κB were increased after 48 h of hyperoxia or LPS exposure compared with control group(P<0.05). However, the mRNA expression of IL-1β, TNF-α and NF-κB were significantly incresead between LPS+hyperoxia group and hyperoxia group(LPS group)(P<0.05).the activity of SOD fell down accordingly in LPS group or hyperoxia group, compared with the control group. Furthermore, our results showed that the protein levels of Iba1 and Caspase3 were increased in hyperoxia group compared with control group, but that doubt increase significantly in LPS+hyperoxia group compared with hyperoxia or LPS group(P<0.05).Conclusion: The overall results demonstrated that infection with systemic inflammation induced premature mice white matter damage. Hyperoxia exposure with this infection could accelerate neuronal apoptosis and delayed oligodendrocyte maturation, which would cause irreversible damage with white matter. It was helpful to understand the pathologic change of premature infants progressively.