Impact Of Postnatal Infection/Inflammations On Progressive White Matter Injury In Premature Mouse

Objectives Preterm infants display a greater propensity for brain injury caused by hypoxic or ischemic events, infection and/or inflammation that results in prominent white matter injury(PWMI),including interuterine infection, sepsis, mengingtis and necrotizing enterocolitis. Injury to the premature brain can substantially influence brain development and lead to disability. Although clinical research provide the proof of concept that systemic inflammation can alter the programming the developing brain,it does not clarity pathophysiological mechanisms, providing behavioral data that allow for a link to the human situation. The purpose of this study is to investigate the oligodendrocyte myelination and neurobehavioral impairment in a postnatal day13(P13) mouse model injected with lipopolysaccharide (LPS). Then, we want to investigate if intrauterine infection can selectively sensitizes white matter injury in the mouse brain followed postnatal LPS-induced.Methods (1)The animals were divided4groups:①control group:the pregnant mice got systemic maternal injection of saline0.05mg/kg at E18; then their offspring were injected intraperitoneally with saline once a day from P3-P12and pups were sacrificed at P13.②intrauterine LPS group:pregnant mice got systemic maternal injection of LPS (Escherichia coli055:B5; Sigma, USA)0.05mg/kg at E18; then their offspring were injected with saline use the same protocol as group1.③postnatal LPS group:mice were injected intraperitoneally with LPS0.05mg/kg once a day from P3-P12.④intrauterine and postnatal LPS group:the pregnant mice got systemic maternal injection of saline0.05mg/kg at E18; then their offspring were injected with LPS use the same protocol as group3.(2) Monitor the body weight once a day from P3to P12in mouse.(3)Pups were sacrificed at P13and brain were collected and weighted.(4) Cresyl violet staining was applied to observe the pathological changes.(5) Brain injury was evaluated by A2B5, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), to investigate the expression of preoligodendrocytes (preOLs), and the expression of oligodendrocytes myelination.(6) The quantity of myeloperoxidase (MPO) in brain homogenate was measured.(7) Behavioral function was evaluated at P7and P13using the behavioral assessment.Results (1)After administration of LPS0.05mg/kg from P3to P12, brain weight was decreased compared with endotoxin-free saline-treated animals. The whole body weight was not difference between groups.(2) There was a significant decline in both cell numbers in animals treated with LPS (P<0.05)。(3)IL-1β was a significant increase was noted in LPS-treated animals compared with saline-treated animals (P<0.05). The density of A2B5-positive cells in the white matter was significantly increased in LPS-treated animals. In contrast, MBP resuls show that there was rarefaction in LPS-treated animals.(4) MPO in the brain was not difference between groups.(5) The time of reflex has significantly increased in LPS-treated animals and associated neonatal brain injury on motion function (P<0.05)Conclusions (1) Neonatal inflammation is an important risk factor for progressive white matter injury in immature brain.(2) Intrauterine and postnatal infection electively sensitizes LPS-induced white matter injury in the immature brain.