The fundamental goal of the Laboratory for Translational Epilepsy Research is to use animal models of epilepsy to further the understanding of basic mechanisms of epilepsy and to translate this understanding to the improvement of treatment of human patients. Much of the laboratory effort is focused on mechanisms and treatment of status epilepticus as a dynamic state.
Experimental and clinical data, mostly generated by Dr. David Treiman and his colleagues over the last 20 years, have demonstrated a series of electroclinical and pathophysiological changes during untreated or inadequately treated generalized status epilepticus. For instance, there is a predictable sequence of progressive EEG changes during GCSE. Growing evidence exists that the EEG stage during SE predicts ease of treatment and long-term consequences. For example, when experimental SE is stopped at SE EEG Stage I or III there is no effect on cognition as tested in a Morris water maze. However, if SE progresses to Stage IV or V there is a profound impairment of memory and learning. Elaboration of these observations and elucidation of their underlying mechanisms is now being pursued in a number of experiments in the laboratory.
One of the consequences of status epilepticus is the subsequent development of chronic epilepsy. In the experimental setting this provides a model for the study of epileptogenesis and its prevention. Using computerized analysis of EEG, we are working to develop reliable predictors of epileptogenesis that could identify animals susceptible to developing chronic epilepsy after brain insult. This identification would allow for early treatment with prophylactic drugs to prevent epileptogenesis in just these animals. These biomarkers of epileptogenesis, once developed and tested in animal models, could lead to greater insights into the underlying mechanisms of epileptogenesis in patients who have suffered status epilepticus or traumatic brain injury, which, in turn, may lead to better agents to prevent epileptogenesis in these situations.
A related focus of the laboratory in this area of inquiry (in collaboration with Leon D. Iasemidis, PhD) is the testing of the efficacy of closed loop feedback control systems, using seizure prediction algorithms and electrical stimulation of selected areas of the brain to prevent seizures in experimental chronic epilepsy in Sprague-Dawley rats. Furthermore, (in collaboration with Lucy J. Treiman, PhD) we recently demonstrated, for the first time in a laboratory model, the efficacy of vagus nerve stimulation (the only FDA approved electrical stimulation therapy for epilepsy) in chronic experimental epilepsy. This observation now provides an animal model for studying optimal parameters for vagus nerve stimulation and for studies of the mechanisms underlying the efficacy of VNS in epilepsy management.
Another line of research being pursued in the laboratory is to noninvasively identify pathological epileptogenic networks on the basis of automated analysis of interictal scalp EEG, and to develop a useful presurgical tool to assist in accurate localization of the seizure focus. Such localization in turn would lead to identification of areas to resect or place implantable stimulators. Our long-term goal is to elucidate the functional mechanisms of brain networks that are involved in the epileptogenic processes in patients and animal models (in vivo and in vitro) and to develop novel therapeutic seizure prevention strategies that can be used to abort seizures and to prevent epilepsy.
Treiman Laboratory Staff
- Shivkumar Sabesan, PhD (Research Bioengineer and Postdoctoral research fellow)
- Steven T. Marsh, BS (Laboratory Technologist)
- Leon D. Iasemidis, PhD (Associate Professor of Bioengineering, Arizona State University, Tempe)
- Rama K. Maganti, MD (Director, EEG Laboratory, Barrow Neurological Institute)
- Jiong Shi, MD, PhD (Director, Cognitive Science Laboratory, Barrow Neurological Institute)
- Lucy J. Treiman, PhD (Director, Behavioral Genetics Laboratory, Barrow Neurological Institute)
- Kostas Tsakalis, PhD (Professor of Electrical Engineering, Arizona State University, Tempe)
- Jie Wu, MD, PhD (Director, Neural Physiology Laboratory, Barrow Neurological Institute)
David M. Treiman, MD
Newsome Chair in Epileptology Director
Barrow Epilepsy Center Principal Investigator