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A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy
Published on: November 3, 2016
Model of cerebral palsy in the perinatal rabbit
Sidhartha Tan1, Alexander Drobyshevsky, Tamas Jilling
1Department of Pediatrics, Northwestern University and Evanston Northwestern Healthcare, Evanston, IL 60201, USA. sidtan@northwestern.edu
Insights
This study developed a rabbit model for prenatal hypoxia-ischemia, mimicking conditions like cerebral palsy. The model revealed lasting motor deficits and brain abnormalities in survivors, highlighting a critical developmental vulnerability.
Area of Science:
- Neuroscience
- Developmental Biology
- Animal Models
Background:
- Perinatal brain injury leads to lifelong disabilities and significant societal costs.
- Cerebral palsy and other neurodevelopmental deficits are often linked to prenatal hypoxia-ischemia.
- Existing animal models do not fully replicate human prenatal hypoxia-ischemia conditions.
Purpose of the Study:
- To develop and validate a novel animal model of in utero sustained and repetitive hypoxia-ischemia in pregnant rabbits.
- To investigate the neurological and motor deficits in postnatal survivors following prenatal insults.
- To establish a reliable model for studying cerebral palsy and related neurodevelopmental disorders.
Main Methods:
- Pregnant rabbits underwent sustained or repetitive hypoxia-ischemia at different gestational ages (22, 25, and 28 days).
- Postnatal survivors were assessed for motor function, reflexes, and sensory responses.
- Magnetic resonance imaging (MRI) was used to evaluate brain abnormalities.
- Artificial feeding was provided to hypertonic survivors to sustain them for observation.
Main Results:
- Hypoxia-ischemia resulted in stillbirths and significant motor deficits in survivors, including impaired locomotion, reflexes, and coordination.
- Hypertonia was observed in survivors from earlier gestational insults (22 and 25 days), persisting for at least 11 postnatal days.
- MRI revealed a spectrum of brain abnormalities in the affected pups.
- This represents the first animal model successfully mimicking key aspects of cerebral palsy.
Conclusions:
- The developed rabbit model effectively mimics human prenatal hypoxia-ischemia and its associated neurodevelopmental deficits, including cerebral palsy.
- The findings indicate a specific window of vulnerability during fetal brain development where injury can lead to hypertonia and persistent motor impairments.
- This model provides a valuable tool for further research into the mechanisms and potential treatments for perinatal brain injury.
Abstract:
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.
