Postnatal inflammatory rat model for cerebral palsy: Too different from humans

Robin Roberson, Jade E. Woodard, Laura Toso, Daniel Abebe, Sarah H. Poggi, Catherine Y. Spong

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Objective: In humans, cerebral palsy (CP) may originate from inflammation during the second and third trimesters of gestation when preoligodendrocytes (Pre-OL) are most vulnerable to an inflammatory insult. We studied a postnatal CP model to evaluate injury that would correlate with presence of Pre-OL in human pregnancy. Study design: On postnatal (P) days 2, 3, 4, 5 and 6, pups were treated with (lipopolysaccharide[LPS]) (n = 7; 30, 30, 60, 60, 120 μg/Kg) or saline (n = 7). Neonates were tested for motor and cognitive development. Adult offspring performed beam walking and rotarod for motor activity. White matter damage was assessed with immunohistochemical Pre-OL markers (CNP, PLP). Statistical analysis included Mann-Whitney U and analysis of variance. Results: LPS-treated animals performed negative geotaxis (P = .009) and surface righting (P = .01) earlier than controls. No differences were observed for other neonatal tests. Adult LPS-treated offspring performed better in tests of motor control: rotarod (P = .01) and beam walking (P = .02). Pre-OL markers were altered in LPS-treated animals at both P22 (CNP and PLP increased in LPS, P < .01 and P < .001, respectively) and 12 weeks (CNP and PLP decreased in LPS, P < .0001 and P < .03, respectively). Conclusion: Neonatal exposure to LPS induced white matter damage in the brain, accelerated neurodevelopment and motor tasks in adulthood. These are similar to findings from a postnatal hypoxic model suggesting that in the rodent, targeting the Pre-OL does not result in a CP phenotype.

Original languageEnglish (US)
Pages (from-to)1038-1044
Number of pages7
JournalAmerican journal of obstetrics and gynecology
Volume195
Issue number4
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Keywords

  • Cerebral palsy
  • Lipopolysaccharide
  • Periventricular leukomalacia
  • Rat

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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