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The Impact Of Seizures On Brain Development Investigators: John W. Swann,
Ph.D. Prior to joining the Baylor faculty, the research in Dr. Swann's laboratory focused on understanding why the immature brain is so susceptible to seizures. While his research at the Cain Laboratories has been influenced by these earlier findings, once he moved to Houston, his efforts focused on more complex mechanisms of epilepsy. The first of these was to determine the impact seizures have on brain development. Nine years ago the consensus from experimental studies in immature animals was that seizures did not effect brain development. However, this conclusion made little sense to the parents of children who were developmentally normal prior to experiencing seizures and whose ability to learn slowed or even stopped once a seizure disorder began. The problem was that there were no animal models that could be used to address this problem. One of our major accomplishments has been the development of such animal models. In these studies, brief recurrent seizures that are common in children with intractable epilepsy are induced in infant rats for one week. We have found that these seizures result in learning deficits. This is a very dramatic effect. While less than half of these animals go on to develop chronic epilepsy, all of them have major problems in learning new task. Seizures were found not to kill developing brain cells. Thus, learning problems cannot be explained by the loss of brain cells. Indeed the brain appears normal in size and overall structure. However, at the microscopic and molecular level, important changes have been observed. Individual nerve cells are missing microscopic structures called dendritic spines. Molecular markers for some synaptic connections are also decreased in the brain. One of these molecules is the NR1 subunit of the NMDA synaptic receptor. This molecule has been implicated in the formation of memories in the brain. Thus, decreases in NMDA receptor could play a key role in learning disorders following seizures in early life. Our planned studies are to determine the biochemical steps leading to alterations in NMDA receptors.
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