TY - JOUR
T1 - Postnatal inflammatory rat model for cerebral palsy
T2 - Too different from humans
AU - Roberson, Robin
AU - Woodard, Jade E.
AU - Toso, Laura
AU - Abebe, Daniel
AU - Poggi, Sarah H.
AU - Spong, Catherine Y.
N1 - Funding Information:
Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development and NIAAA.
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
KW - Cerebral palsy
KW - Lipopolysaccharide
KW - Periventricular leukomalacia
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=33748759850&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748759850&partnerID=8YFLogxK
U2 - 10.1016/j.ajog.2006.06.046
DO - 10.1016/j.ajog.2006.06.046
M3 - Article
C2 - 17000237
AN - SCOPUS:33748759850
SN - 0002-9378
VL - 195
SP - 1038
EP - 1044
JO - American journal of obstetrics and gynecology
JF - American journal of obstetrics and gynecology
IS - 4
ER -