Optogenetic Intervention of Posttraumatic Epilepsy
Abstract
The goal of our research is to understand the process of new neuron formation after traumatic brain injury commonly experienced by military personnel, a process called "adult hippocampal neurogenesis." While it is believed a population of healthy neurons is generated after traumatic brain injury, possibly as a repair mechanism, in the hippocampus (a region responsible for learning and memory in the brain), there is the formation of abnormal neurons called "aberrant neurogenesis." It is thought these new neurons trigged by brain injury forms aberrant connections with other neurons, disrupting normal circuits and causing epilepsy. We are trying to understand how aberrant neurogenesis after traumatic brain injury contributes to the recurrence of seizures and associated memory problems, which are long-term side effects of some patients after combat. In order to identify the causative role of chronic epilepsy after traumatic brain injury (post-traumatic epilepsy), we developed an animal model of human post-traumatic epilepsy by using inbred mice induced with brain damage. In our proposal, we will combine our mouse model of post-traumatic epilepsy model with a genetic system to kill (or ablate) just the newly generated neurons (without affecting the pre-existing mature neurons and glial cells). We will also take a second, innovative new approach called "optogenetics," which uses light to temporarily silence neuronal activity. In this manner, we will study whether epileptic mice with reduced aberrant neurogenesis showed fewer recurrent seizures upon electroencephalogram (EEG) monitoring. In addition, common side effects in patients with post-traumatic epilepsy are memory problems and mood changes. Therefore, preventing the cognitive decline associated with epilepsy would represent a significant step forward for patients with epilepsy. Taken together, our studies will provide a basis for the treatment of epileptic seizures and associated cognitive decline by presenting abnormal neurogenesis as a clinically applicable target.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510399
Entities
People
- Jenny Hsieh
Organizations
- United States Army
- University of Texas Southwestern Medical Center