title: Inflammatory-mediated model of cerebral palsy with developmental sequelae.
abstract: OBJECTIVE
  Cerebral palsy (CP) is characterized by motor deficits. There is increasing evidence that CP may result from inflammatory and infection-mediated white matter damage. Our objective was to develop an inflammatory model for CP based on chronic lipopolysaccharide (LPS) exposure with a recognizable phenotype in offspring.
  
  
  METHODS
  On gestational days 15, 17, and 19 (approximately 28-36 wks human gestation; rat length of gestation is 21 days), pregnant rats were intracervically injected with 0.15 mg/kg LPS (in 0.1 mL saline) or 0.1 mL saline for controls. Neonatal tests for sensory-motor milestones were performed on postnatal days 1 to 21 (LPS n = 25; control n = 26). Adult males were tested at 8 weeks on open field and rotarod for motor activity. Immunohistochemistry studies were performed to assess olygodendrocyte (OL) damage. Statistical analysis included Mann-Whitney U and analysis of variance (ANOVA) with P < .05 considered significant.
  
  
  RESULTS
  Immunohistochemistry revealed a decrease in the immature OL marker PLP on day 21 (P = .03) in LPS-exposed offspring, and an increase of the mature OL marker CNP on day 21 and at 8 weeks (P < .01, P < .001). LPS-exposed offspring were delayed achieving 3 motor milestones: negative geotaxis (P < .05), cliff aversion (P < .01), and surface righting (P = .05). They were also delayed in eye opening (P < .01). There was no difference between the 2 groups for the other tests. There was a trend towards decreased mean speed in LPS-exposed adults in open field testing (P = .08), but no differences observed in rotarod testing.
  
  
  CONCLUSIONS
  Using an animal model for CP that mimics a chronic intrauterine inflammation that results in decreased levels of PLP, a marker for early oligodendrocytes consistent with white matter damage, we have demonstrated a phenotype relevant to the human CP manifestations in the neonatal period. Nevertheless, adult animals were able to compensate to the damage. Further refinement is needed to improve the understanding of pathogenesis, as well as allow for testing preventative therapies.
authors.affiliation: Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development; National Institute of Health, Bethesda, MD 20892-0925, USA. laura_toso@hotmail.com
authors.forename: Laura
authors.initials: L
authors.lastname: Toso
authors.forename: Sarah
authors.initials: S
authors.lastname: Poggi
authors.forename: Jane
authors.initials: J
authors.lastname: Park
authors.forename: Haim
authors.initials: H
authors.lastname: Einat
authors.forename: Robin
authors.initials: R
authors.lastname: Roberson
authors.forename: Veronica
authors.initials: V
authors.lastname: Dunlap
authors.forename: Jade
authors.initials: J
authors.lastname: Woodard
authors.forename: Daniel
authors.initials: D
authors.lastname: Abebe
authors.forename: Catherine Y
authors.initials: CY
authors.lastname: Spong
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002547:Cerebral Palsy / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D009043:Motor Activity; D009836:Oligodendroglia; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D008070:Lipopolysaccharides