Adult-Born Neurons and the Development of Posttraumatic Epilepsy
Technical Report,01 Sep 2018,31 Aug 2019
OREGON HEALTH and SCIENCE UNIVERSITY PORTLAND United States
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Post-traumatic epilepsy PTE occurs in over 50 of veterans with a history of penetrating head injury, and individuals with severe head injuries have a seventeen-fold increased risk of developing epilepsy later in life. Although PTE is a heterogeneous condition with multiple etiologies, clinical data suggest that it often involves seizure foci in the temporal lobe, and in particular from within the hippocampus. The hippocampus manifests numerous anatomical changes in epilepsy, which are thought to mediate its contribution to neuronal hyperexcitability and seizures. Although the neuroanatomical changes associated with epilepsy are well described, how these abnormalities lead to the development of epilepsy are unknown. This CDMRP project is analyzing whether newly generated neurons in the hippocampus contribute to the formation of hyperexcitable circuits in a mouse model of posttraumatic epilepsy PTE. The projects specific aims are 1 to assess adult-born hippocampal granule cell contributions to the formation of recurrent excitatory brain circuits after traumatic brain injury TBI 2 to characterize network properties of circuits involving adult-born granule cells after TBI and 3 to assess whether modulation of post traumatic neurogenesis by diazepam prevents hippocampal hyperexcitability and posttraumatic epilepsy. If successful, we will not only substantially increase our understanding of how hippocampal function has changed after TBI, but we will also investigate the potential of pharmacologic modulation of the re-wiring process to reduce the subsequent development of epilepsy. This would have great translational relevance to future human clinical trials, which is a major focus of our work.
- Medicine and Medical Research