Effects of bacterial lipopolysaccharide and normobaric hyperoxia on immature brain development of neonatal rat

Abstract

Objective To investigate the effects of lipopolysaccharide(LPS) and / or normobaric hyperoxia on brain development of neonatal rat and the possible mechanisms. Methods One hundred and twenty postnatal day 2 (P2) SD rats were randomly assigned into 4 groups: air group, LPS group, hyperoxia group, LPS + hyperoxia group.General condition and body weight of the rats in each group were observed and recorded every day.The expression of active Caspase-3 and nuclear factor-κappaB P65(NF-κB P65) in the brain were detected by immunohistochemistry staining on P7, and the level of IL-6 and 8-iso-PGF2α in the brain homogenate were measured by enzyme-linked immunosorbent assay(ELISA). The expression of myelin basic protein (MBP) in the brain was detected by immunohistochemistry staining on P12. Results The expressions of Caspase-3 and NF-κB P65 had the same trends: the number of positive cells from high to low was in LPS+ hyperoxia group, LPS group/hyperoxia group, air group.There were significant differences between the first three groups and air group(all P<0.05). There were also significant differences between LPS+ hyperoxia group and LPS group or hyperoxia group(all P<0.01). MBP in the brain had the completely reverse expression: from high to low order was in air group, hyperoxia group, LPS group, LPS+ hyperoxia group.There were significant differences between the last three groups and air group(all P<0.05). There were also significant differences between LPS+ hyperoxia group and LPS group or hyperoxia group(all P<0.01). The level of IL-6 in the brain from high to low order respectively was in LPS+ hyperoxia group, LPS group, hyperoxia group, air group; and 8-iso-PGF2α was also in LPS+ hyperoxia group, hyperoxia group, LPS group, air group, Significant differences were found among the four groups(all P<0.05). Conclusions Both postnatal infection and normobaric hyperoxia may induce premature rat brain injury, and increase the number of apoptosis cell and reduce the expression of MBP.The combination of infection and normobaric hyperoxia may aggravate the degree of brain damage of neonatal rat.NF-κB pathway mediated by Toll-like receptor may be involved in inflammation and oxidative stress, and may mediate Caspase-3 related apoptosis of nerve cell and white matter injury. Key words: Lipopolysaccharide; Normobaric hyperoxia; 8-iso-PGF2α; Nuclear factor-κ appaB P65; Myelin basic protein