Traumatic brain injury (TBI) leads to severe and lasting disabilities in sensorimotor and cognitive functions in 30,000 to 50,000 people in the United States each year. Approximately one third of individuals with serious head injuries eventually develop epilepsy. As TBI largely afflicts young people, health care and lost income are more costly than for stroke or degenerative diseases that typically affect the elderly. Clearly, interventions to prevent epilepsy, while promoting recovery from primary deficits after TBI, would be of great social value. Accordingly, this proposal examines the development of epileptogenic cellular physiology in rat sensorimotor cortex after a controlled injury, using a combination of extra-and intracellular electrophysiolgy, voltage- and calcium imaging, and histological methods. The experiments will also include an examination of the neuromodulatory role of noradrenaline (NA) after TBI for two reasons. First, NA plays a complex role in both suppressing and promoting epileptogenesis. Second, NA with physical therapy (NA/PT) is the only pharmacotherapy that has enhanced functional recovery in double-blind studies of patients with well-established brain injury. This proposal represents a synthesis of my ongoing interest in basic mechanisms of epilepsy (which I have explored in hippocampus) and my career goal of expanding my area of research to include the neocortex, intracellular electro-and calcium physiology, and pathophysiology of head trauma. This project, including the mentorship of J.A. Connor and the collaboration of D.M. Feeney and R.C. S. Lin, will allow me to establish myself in these new areas, wile drawing on my experience with the kindling and kainate models of epilepsy, with various histological methods, with electrophysiolgy in vivo, and with the voltage-imaging techniques that I have learned with J.A. Connor. I will work with three senior scientists who have made major contributions to the fields of neuronal calcium and electrophysiology (Connor), TBI and NA/PT (Feeney) and anatomical correlates of neuopathophysiology (Lin). This rare interdisciplinary research opportunity will allow me to contribute to the understanding of post-traumatic epilepsy while increasing my breadth and depth as a scientist.
| Golarai, G; Greenwood, A C; Feeney, D M et al. (2001) Physiological and structural evidence for hippocampal involvement in persistent seizure susceptibility after traumatic brain injury. J Neurosci 21:8523-37 |
