Hypoxic-Ischemic Encephalopathy (HIE) is the brain manifestation of systemic asphyxia which occurs in 20 out of 1000 births. 25% of neonates who suffer from HIE exhibit severe permanent neuropsychological handicaps in the form of cerebral palsy, with or without associated mental retardation, learning disabilities, or epilepsy. Due to the devastating consequences of HIE, much research has focused on interrupting the cascade of events which are triggered by HIE. In the lab, these therapies have shown mixed results in limiting neuronal injury when given before or after the hypoxic-ischemic insult. These therapies have met with even more limited success in the clinical environment and the clinician's main armamentarium still remains supportive care. Stem cell therapy offers an attractive therapy for HIE. The ability to replace necrotic cells with functional cells would potentially limit the degree of long term neurological deficits. This therapy is particularly suited to the neonate due to the continued division of cells in the subventricular zones of the developing brain. This division essentially leaves intact chemical and cellular sign posts for the implanted stem cells to migrate and differentiate. Based on the fertile milieu in the developing brain, we hypothesize that stem cells implanted into the ventricles of neonatal mouse pups following hypoxic-ischemic brain injury will migrate to the area of injury and differentiate. The proposed hypothesis will be tested by using a mouse model of HIE. Following injury, stem cells will be implanted into the injured animal in either the lateral ventricle or injured cortex at 24 hours and 7 days post injury. Brains will then be collected 7-14 days post transplant. The location, cell type, and degree of differentiation of the transplanted stem cells will be analyzed. Axonal tracing studies will also be performed to begin to understand the physiologic activity of the implanted cells. Hypoxic-Ischemic Encephalopathy (HIE) is the brain manifestation of systemic asphyxia which occurs in 20 out of 1000 births. 25% of neonates who suffer from HIE exhibit severe permanent neuropsychological handicaps in the form of cerebral palsy, with or without associated mental retardation, learning disabilities, or epilepsy. This project begins to explore a potential therapy, stem cell transplants, for HIE using an animal model. ? ? ?
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