Postnatal inflammatory rat model for cerebral palsy: too different from humans.
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.


METHODS
On postnatal (P) days 2, 3, 4, 5 and 6, pups were treated with (lipopolysaccharide [LPS]) (n = 7; 30, 30, 60, 60, 120 microg/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).


CONCLUSIONS
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.
Roberson
Robin
R
Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Woodard
Jade E
JE
Toso
Laura
L
Abebe
Daniel
D
Poggi
Sarah H
SH
Spong
Catherine Y
CY
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002547:Cerebral Palsy / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications*; D008070:Lipopolysaccharides / Q000633:toxicity; D018991:Myelin Proteolipid Protein / Q000032:analysis; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity
D008070:Lipopolysaccharides; D018991:Myelin Proteolipid Protein; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases