Periodic lateralized epileptiform discharges (PLEDs) are an electroencephalographic pattern seen in humans following cerebral injury associated ischemia, infection, and status epilepticus. Patients with PLEDs suffer severe neurologic dysfunction. However, despite the 60-80% morbidity and mortality associated with PLEDs, we know little about the natural history, pathophysiology, and treatment of PLEDs. We propose to test the hypothesis that the PLEDs have prognostic and pathophysiological importance.
The Specific Aims of this proposal include 1) screening for NMDA receptor antagonists to treat PLEDs utilizing an in-vitro hippocampal slice model and 2) correlating the severity of PLEDs with hippocampal cell loss and onset to epilepsy using a whole-animal model. This proposal describes a 5-year training program to investigate cellular mechanisms underlying PLEDs. The principal investigator has completed her Neurology residency and clinical Neurodiagnostics fellowship at the University of Colorado Health Sciences Center (UCHSC). She embarked upon a research career with support from the Epilepsy Foundation of America """"""""Clinical Training Fellowship"""""""" and will now prepare for an academic career by expanding her scientific skills. Mentors for the laboratory research training are 1) Kevin J. Staley, MD, Chief of Neurology at The Children's Hospital and an authority in the field of the cellular mechanisms of epilepsy and 2) F. Edward Dudek, PhD, Professor, Department of Biomedical Sciences, Colorado State University (CSU), a distinguished leader in synaptic and non-synaptic neurophysiology and whole animal models of epilepsy. To supplement the laboratory research, the principle investigator will enroll in graduate-level didactic coursework in Neuroscience and Clinical Sciences (e.g. biostatistics, ethics and research methods). To enhance clinical and teaching skills, she will provide in- and out-patient neurological care and supervise students and house-staff (10 - 15% time) at University Hospital. An advisory committee of medical scientists from the Neuroscience Program at UCHSC will provide career and scientific advice to the principle investigator. The goal of this proposal is to provide new technical skills, scientific knowledge, and rigorous academic training to launch the principle investigator's independent research career. The long-term goal is to understand the cellular mechanisms that govern PLEDs, which will lead to experiments designed to treat epileptic activity and improve outcomes for individuals with this grave condition.
| Diao, Lihong; Hellier, Jennifer L; Uskert-Newsom, Jessica et al. (2013) Diphenytoin, riluzole and lidocaine: three sodium channel blockers, with different mechanisms of action, decrease hippocampal epileptiform activity. Neuropharmacology 73:48-55 |
