Model of cerebral palsy in the perinatal rabbit.
Perinatal brain injury results in one of the highest burdens of disease in view of the lifelong consequences and is of enormous cost to society. This makes it imperative to develop better animal models that mimic the human condition. Many neurodevelopmental deficits, such as cerebral palsy, are believed to be a result of prenatal hypoxia-ischemia in humans. Fetal global hypoxia-ischemia is most commonly a consequence of acute placental insufficiency. Our laboratory has modeled in utero sustained and repetitive hypoxia-ischemia in the pregnant rabbit to mimic the insults of abruptio placenta and labor, respectively. Sustained hypoxia-ischemia at 70% (22 days' gestation) and 79% (25 days' gestation) and repetitive hypoxia-ischemia at 90% gestation (28 days' gestation) caused stillbirths and multiple deficits in the postnatal survivors. The deficits included impairment in multiple tests of spontaneous locomotion, reflex motor activity, motor responses to olfactory stimuli, and the coordination of suck and swallow. Hypertonia was observed in the 22 and 25 days' gestation survivors but not in the 28 days' gestation group. Hypertonic survivors were artificially fed and found to have the motor deficits persist for at least 11 postnatal days. A spectrum of brain abnormalities is found on magnetic resonance imaging. This is the first animal model to mimic cerebral palsy. The findings also suggest a window of vulnerability during brain development when the injury results in hypertonia in newborn pups.
Tan
Sidhartha
S
Department of Pediatrics, Northwestern University and Evanston Northwestern Healthcare, Evanston, IL 60201, USA. sidtan@northwestern.edu
Drobyshevsky
Alexander
A
Jilling
Tamas
T
Ji
Xinhai
X
Ullman
Lauren M
LM
Englof
Ila
I
Derrick
Matthew
M
D000037:Abruptio Placentae; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000150:complications / Q000662:veterinary; D002547:Cerebral Palsy / Q000503:physiopathology* / Q000662:veterinary; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D002534:Hypoxia, Brain / Q000150:complications / Q000662:veterinary; D009122:Muscle Hypertonia; D011247:Pregnancy