title: N-acetylcysteine attenuates the maternal and fetal proinflammatory response to intrauterine LPS injection in an animal model for preterm birth and brain injury.
abstract: OBJECTIVE
  Maternal immune activation (MIA) is associated with preterm birth (PTB) and abnormal neurologic outcome. We hypothesized that N-acetylcysteine (NAC) would decrease PTB and neonatal brain injury acting as an anti-inflammatory.
  
  
  METHODS
  Pregnant CD-1 mice received intrauterine LPS or saline on day 15/20. They received NAC or saline and were monitored until delivery. Pups were followed and sacrificed on postnatal days 1/30 and brains were collected. Immunostaining for heavy-chain neurofilament protein (NF-H), myelin basic protein (MBP), and proteolipid protein (PLP) was performed. In another group, animals were sacrificed 6 h after treatment, and fetal brain, placenta, and myometrium were collected. Il-6, Il-1β, Il-10, and tumor necrosis factor (TNF)-α mRNA expression was determined. Nonparametric analysis was used for analysis, and pairwise comparisons were performed when appropriate.
  
  
  RESULTS
  Lipopolysaccharide (LPS) caused PTB (79 vs. 0%, p < 0.005), and this was reduced by NAC [0.45 (95% CI: 0.26-0.83), p < 0.008]. LPS increased IL-6 expression in myometrium and placenta. This was attenuated by NAC in myometrium. IL-1β, IL-6, and TNF-α expression increased in the fetal brain with LPS. LPS produced altered NF-H, MBP, and PLP staining, and these effects were attenuated by NAC.
  
  
  CONCLUSIONS
  NAC attenuates inflammation in this MIA model and reduces PTB and white matter injury. It is an interesting candidate for study for prevention of PTB and neurologic injury.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC 29425, USA. changey@musc.edu
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Chang
authors.forename: Jingmei
authors.initials: J
authors.lastname: Zhang
authors.forename: Scott
authors.initials: S
authors.lastname: Sullivan
authors.forename: Roger
authors.initials: R
authors.lastname: Newman
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005315:Fetal Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D051379:Mice; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology / Q000517:prevention & control*
chemical_list: D016166:Free Radical Scavengers; D000111:Acetylcysteine