Mechanism and Therapy for the Shared Susceptibility to Migraine and Epilepsy after Brain Injury (TBI)
Abstract
Our proposal has examined the natural history and mechanisms of increased brain excitability leading to migraine and epilepsy after traumatic brain injury (TBI). In order to pursue our work, we have pioneered or significantly advanced new techniques for the study of TBI, including continuous remote telemetry, in vivo whole cell recording, and two-photon imaging with genetically encoded calcium indicators. We have generated multiple reportable outcomes, providing experimental evidence that: 1. TBI causes seizures; 2. TBI increases neuronal excitability, an effect that is enhanced in migraine mutant mice; 3. TBI is universally associated with spreading depolarization that are also involved in migraine; 4. sensory cortex is more susceptible to spreading depolarizations, consistent with prominent sensory and pain features after TBI; 5. the effects of TBI are amplified by female sex as well as migraine genotype, consistent with what is observed in the clinic. We have published four manuscripts (in Science Translational Medicine, Stroke, Journal of Neurophysiology, and Cephalalgia); two more are pending publication; and four more manuscripts are in preparation. This work also continues in CDMRP PR130373.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2015
- Accession Number
- AD1005276
Entities
People
- Dan Kaufmann
- Ed Dudek
- Jeremy Theriot
- K. C. Brennan
- Punam Sawant
Organizations
- University of Utah