Clinical Focus

  • Epilepsy

Academic Appointments

Professional Education

  • Residency: Stanford University Dept of Neurology (1996) CA
  • Fellowship: Stanford University Epilepsy Fellowship (2000) CA
  • Internship: Indiana University Transitional Year (1993) IN
  • Board Certification: American Board of Psychiatry and Neurology, Epilepsy (2013)
  • Board Certification: American Board of Psychiatry and Neurology, Neurology (1999)
  • Medical Education: Indiana University School of Medicine (1992) IN

2023-24 Courses

All Publications

  • A critical period for prevention of posttraumatic neocortical hyperexcitability in rats ANNALS OF NEUROLOGY Graber, K. D., Prince, D. A. 2004; 55 (6): 860-870


    Penetrating cortical trauma frequently results in delayed development of epilepsy. In the rat undercut model of neocortical posttraumatic hyperexcitability, suppression of neuronal activity by exposing the injured cortex to tetrodotoxin (TTX) in vivo for approximately 2 weeks prevents the expression of abnormal hypersynchronous discharges in neocortical slices. We examined the relationship between neuronal activity during the latent period after trauma and subsequent expression of hyperexcitability by varying the timing of TTX treatment. Partially isolated islands of rat sensorimotor cortex were treated with Elvax polymer containing TTX to suppress cortical activity and slices obtained for in vitro experiments 10 to 15 days later. TTX treatment was either started immediately after injury and discontinued after a variable number of days or delayed for a variable time after the lesion was placed. Immediate treatment lasting only 2 to 3 days and treatment delayed up to 3 days prevented hyperexcitability. Thus, there is a critical period for development of hyperexcitability in this model that depends on cortical activity. We propose that the hyperexcitability caused by partial cortical isolation may represent an early stage of posttraumatic epileptogenesis. A hypothetical cascade of events leading to subsequent pathophysiological activity is likely initiated at the time of injury but remains plastic during this critical period.

    View details for DOI 10.1002/ana.20124

    View details for Web of Science ID 000221716300013

    View details for PubMedID 15174021

  • Postlesional epilepsy: The ultimate brain plasticity 5th Workshop on the Neurobiology of Epilepsy (WONOEP V) Jacobs, K. M., Graber, K. D., Kharazia, V. N., Parada, I., Prince, D. A. WILEY-BLACKWELL. 2000: S153–S161


    Lesions that occur either during fetal development or after postnatal brain trauma often result in seizures that are difficult to treat. We used two animal models to examine epileptogenic mechanisms associated with lesions that occur either during cortical development or in young adults. Results from these experiments suggest that there are three general ways that injury may induce hyperexcitability. Direct injury to cortical pyramidal neurons causes changes in membrane ion channels that make these cells more responsive to excitatory inputs, including increases in input resistance and a reduction in calcium-activated potassium conductances that regulate the rate of action potential discharge. The connectivity of cortical circuits is also altered after injury, as shown by axonal sprouting within pyramidal cell intracortical arbors. Enhanced excitatory connections may increase recurrent excitatory loops within the epileptogenic zone. Hyperinnervation attributable to reorganization of thalamocortical, callosal, and intracortical circuitry, and failure to prune immature connections, may be prominent when lesions affect the developing neocortex. Finally, focal injury can produce widespread changes in gamma-aminobutyric acid and glutamate receptors, particularly in the developing brain. All of these factors may contribute to epileptogenesis.

    View details for Web of Science ID 000089156500028

    View details for PubMedID 10999537

  • Tetrodotoxin prevents posttraumatic epileptogenesis in rats ANNALS OF NEUROLOGY Graber, K. D., Prince, D. A. 1999; 46 (2): 234-242


    Severe cortical trauma frequently causes epilepsy that develops after a long latency. We hypothesized that plastic changes in excitability during this latent period might be initiated or sustained by the level of neuronal activity in the injured cortex. We therefore studied effects of action potential blockade by application of tetrodotoxin (TTX) to areas of cortical injury in a model of chronic epileptogenesis. Partially isolated islands of sensorimotor cortex were made in 28- to 30-day-old male Sprague-Dawley rats and thin sheets of Elvax polymer containing TTX or control vehicle were implanted over lesions. Ten to 15 days later neocortical slices were obtained through isolates for electrophysiological studies. Slices from all animals (n = 12) with lesions contacted by control-Elvax (58% of 36 slices) exhibited evoked epileptiform field potentials, and those from 4 rats had spontaneous epileptiform events. Only 2 of 11 lesioned animals and 6% of slices from cortex exposed to TTX in vivo exhibited evoked epileptiform potentials, and no spontaneous epileptiform events were observed. There was no evidence of residual TTX during recordings. TTX-Elvax was ineffective in reversing epileptogenesis when implanted 11 days after cortical injury. These data suggest that development of antiepileptogenic drugs for humans may be possible.

    View details for Web of Science ID 000081876900013

    View details for PubMedID 10443889