title: Effect of sustained postnatal systemic inflammation on hippocampal volume and function in mice.
abstract: BACKGROUND
  Premature infants are at risk for persistent neurodevelopmental impairment. Children born preterm often exhibit reduced hippocampal volumes that correlate with deficits in working memory. Perinatal inflammation is associated with preterm birth and brain abnormalities. Here we examine the effects of postnatal systemic inflammation on the developing hippocampus in mice.
  
  
  METHODS
  Pups received daily intraperitoneal injections of lipopolysaccharide (LPS) or saline between days 3 and 13. Ex vivo magnetic resonance imaging (MRI) and microscopic analysis of brain tissue was performed on day 14. Behavioral testing was conducted at 8-9 wk of age.
  
  
  RESULTS
  MR and microscopic analysis revealed a 15-20% reduction in hippocampal volume in LPS-treated mice compared with controls. Behavioral testing revealed deficits in hippocampal-related tasks in LPS-treated animals. Adult mice exposed to LPS during the postnatal period were unable to select a novel environment when re-placed within a 1-min delay, were less able to remember a familiar object after a 1-h delay, and had impaired retention of associative fear learning after 24 h.
  
  
  CONCLUSIONS
  Systemic inflammation sustained during the postnatal period contributes to reduced hippocampal volume and deficits in hippocampus-dependent working memory. These findings support the novel and emerging concept that sustained systemic inflammation contributes to neurodevelopmental impairment among preterm infants.
authors.affiliation: Department of Pediatrics, The Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts.
authors.forename: Shadi N
authors.identifier: 0000000165235984
authors.initials: SN
authors.lastname: Malaeb
authors.affiliation: Department of Pediatrics, The Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Davis
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.
authors.forename: Ilka M
authors.initials: IM
authors.lastname: Pinz
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Newman
authors.affiliation: 1] Department of Public Health & Community Medicine, Tufts University School of Medicine, Boston, Massachusetts [2] Department of Obstetrics and Gynecology Perinatal Neuroepidemiology Unit, Hannover Medical School, Hannover, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dammann
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Maribel
authors.initials: M
authors.lastname: Rios
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D003071:Cognition; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D045442:Rotarod Performance Test