| Objective Periventricular leukomalacia (PVL), a common neonatal brain white matter damage (WMD), is frequently known as an important reason to cerebral palsy. Growing evidences have indicated that besides ischemia/reperfusion injury, cytokine-induced brain injury associated maternal or fetal infection may also play a key role in the pathogenesis of PVL. Abundant studies have shown that administration of lipopolysaccharide (LPS) to pregnant rats could induce expression of some proinflammatory cytokines in fetal brains. In recent years, it has been shown that DHA has a critical role in the development, protection and repair of the nervous system. In the present study, we observe the dynamic changes of microglia, IL-1βand MyD88 in the brain tissue of rat pups after intrauterine LPS expose, and compare with the changes of DHA/LPS expose, and then evaluate the effects of DHA on LPS-induced brain inflammation.Methods Pregnant Sprague-Dawley rats were divided into three groups: control group, LPS-treated group and DHA-treated group. LPS (350μg/kg body weight) was administered intraperitoneally to pregnant rats at 17 and 18 days of gestation while the control group was treated with pyrogen free saline. Since the first day of gestation,DHA (140mg/kg) was given to the pregnant rats of DHA-treated group by intragastric administration every day, while the other two groups were administrated pyrogen free water. The brains of rat pups were reserved at 21 day of gestation by uterine-incision delivery (G21), and at postnatal 1, 7, 14 days (P1, P7, P14), and the placenta of new borns were kept. Cytokine IL-1βinductions in the rat pups brain were determined by the Western-blotting and real-time quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) methods. OX42 monopoly antibody was used to detect activated microglia by immunohistochemical method. The mRNA of Myd88 was determined by Q-RT-PCR methods. The placenta and brain injury were observed by pathological section with hematoxylin-eosin (HE) staining method.Results Pregnant rats of each group had normal activity and feeding after intraperitoneal injection. In the LPS-treated group, one pregnant rat was dead, one was abortion, and two pregnant rats were premature delivery and a part of their offspring had already dead. The mean birth weight of the rat pups in the LPS-treated group was significant lower than the control group and DHA-treated group (p<0.05), the hematoxylin-eosin (HE) stained placenta sections showed remarkable interstitial hyperplasia, narrow capillary and inflammatory infiltration, and brain HE stained sections showed cellular edema, tissue rarities and cell population decreased. In DHA-treated group, only one pregnant rat was abortion, none of them was dead, the placentas showed less inflammatory cells infiltration, and had rich blood supply. The control group showed nothing abnormal. Compared with control group: 1) The IL-1βmRNA expressions in brain tissue were increased remarkably till P14 in LPS-treated group (p<0.05), but increased slightly in DHA-treated group till P7 (p<0.05). 2) The IL-1βprotein secretions were increased remarkably till P14 in LPS-treated group (p<0.05), but increased slightly in DHA-treated group before P7 (p<0.05). 3)The mRNA expression of MyD88 increased significantly at G21 and P1 in LPS-treated group and DHA-treated group (p<0.05). 3) Up to P14, OX42 positive microglias increased constantly in LPS-treated group (p<0.05), in DHA-treated group which increased till P7 (p<0.05), but there were little diffirence at P14.Conclusions Intraperitoneal LPS (350μg/kg body weight) administration to pregnant rats induced an inflammatory response of placenta and fetus, finally resulted in brain injury. Maternal DHA treatment during pregnancy attenuates LPS-induced intrauterine and fetus brain inflammation by reducing the persistent expression of inflammatory cytokine IL-1βand microglia activation in the neonatal rat brain, then promoting the injury recover and the nervous system development.
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