Postnatal inflammatory rat model for cerebral palsy: Too different from humans - 19/08/11
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.
Le texte complet de cet article est disponible en PDF.Key words : Cerebral palsy, Periventricular leukomalacia, Lipopolysaccharide, Rat
Plan
| Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development and NIAAA. Presented at the 26th Annual Meeting of the Society for Maternal Fetal Medicine, January 30-February 4, 2006, Miami, FL. Reprints not available from the authors. |
Vol 195 - N° 4
P. 1038-1044 - octobre 2006 Retour au numéro
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