title: Intracerebral lipopolysaccharide induces neuroinflammatory change and augmented brain injury in growth-restricted neonatal rats.
abstract: BACKGROUND
  Intrauterine growth restriction (IUGR) alters fetal development and is associated with neurodevelopmental abnormalities. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to subsequent inflammatory brain injury.
  
  
  METHODS
  In this study, IUGR was achieved by induced placental insufficiency in pregnant rats at 14 days of gestation. IUGR offspring and sham-operated control pups were subsequently injected with intracerebral lipopolysaccharide (LPS) as a model of periventricular leukomalacia (PVL).
  
  
  RESULTS
  LPS similarly elevates proinflammatory cytokines in the brains of both IUGR and control rat pups. However, the chemokines cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage chemoattractant protein-1 (MCP-1), as well as microglia activation, were significantly higher in LPS-treated IUGR rat pups as compared with LPS-treated controls. In addition to the unique brain inflammatory response, IUGR rat pups demonstrated increased brain damage with an increased number of apoptotic cells, larger lateral ventricular size, and more severe impairment of myelination.
  
  
  CONCLUSIONS
  This study provides evidence that placental insufficiency may sensitize the innate immune system in the immature brain and reveals a possible link between brain inflammation and injury.
authors.affiliation: Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. lrcampbell@umc.edu
authors.forename: Leigh R
authors.initials: LR
authors.lastname: Campbell
authors.forename: Yi
authors.initials: Y
authors.lastname: Pang
authors.forename: Norma B
authors.initials: NB
authors.lastname: Ojeda
authors.forename: Baoying
authors.initials: B
authors.lastname: Zheng
authors.forename: Philip G
authors.initials: PG
authors.lastname: Rhodes
authors.forename: Barbara T
authors.initials: BT
authors.lastname: Alexander
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D017209:Apoptosis; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D004678:Encephalomalacia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007231:Infant, Newborn; D007276:Injections, Intraventricular; D007969:Leukomalacia, Periventricular / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects*; D010927:Placental Insufficiency / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D008070:Lipopolysaccharides