A model of cerebral palsy from fetal hypoxia-ischemia.
Disorders of the maternal-placental-fetal unit often results in fetal brain injury, which in turn results in one of the highest burdens of disease, because of the lifelong consequences and cost to society. Investigating hypoxia-ischemia in the perinatal period requires the factoring of timing of the insult, determination of end-points, taking into account the innate development, plasticity, and enhanced recovery. Prenatal hypoxia-ischemia is believed to account for a majority of cerebral palsy cases. We have modeled sustained and repetitive hypoxia-ischemia in the pregnant rabbit in utero to mimic the insults of abruptio placenta and labor, respectively. Rabbits have many advantages over other animal species; principally, their motor development is in the perinatal period, akin to humans. Sustained hypoxia-ischemia at 70% (E22) and 79% (E25) 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 E22 and E25 survivors and persisted for at least 11 days. Noninvasive imaging using MRI suggests that white matter injury in the internal capsule could explain some of the hypertonia. Further investigation is underway in other vulnerable regions such as the basal ganglia, thalamus and brain stem, and development of other noninvasive determinants of motor deficits. For the first time critical mechanistic pathways can be tested in a clinically relevant animal model of cerebral palsy.
Derrick
Matthew
M
Department of Pediatrics, Northwestern University and Evanston Northwestern Healthcare, Evanston, IL 60201, USA.
Drobyshevsky
Alexander
A
Ji
Xinhai
X
Tan
Sidhartha
S
D000818:Animals; D001921:Brain / Q000473:pathology; D002547:Cerebral Palsy / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005311:Fetal Hypoxia / Q000175:diagnosis / Q000503:physiopathology*; D011247:Pregnancy; D011817:Rabbits