Most partial epilepsies are acquired through brain injury and subsequent development of hyperexcitability by a process of epileptogenesis. My laboratory is studying the underlying mechanisms of how this hyperexcitability develops in a previously normal brain. Since the abnormal hyperexcitability lasts a lifetime, altered gene expression may be one mechanism by which this occurs. As seizures induce immediate-early genes, such as c-fos and c-jun, they may be an initial trigger of a multitude of cellular processes involved in the process. Using hippocampal explant slice cultures, we are using antisense oligonucleotide methodology to suppress the gene expression induced by epileptic or excitotoxic stimulation in this culture system and examine for protective effect. We are also using intraventricular antisense to see if seizure induced damage can be reduced.
Another area of interest is the study of mechanisms of vitamin D neuroprotection. Using the hippocampal explant cultures and in vivo mice with vitamin D receptor gene knockout, we are examining the NGF-mediated pathways of vitamin D effect in the CNS.
Clinical Practice, Interests, and Accomplishments
Clinical Epilepsy (Mayo Clinic Hospital, Methodist Campus Epilepsy Monitoring Unit, Mayo Clinic Hospital, Saint Marys Campus Epilepsy Consulting Service and Epilepsy Outpatient Clinic on W8B); Medical and surgical approach to intractable epilepsies; Investigational antiepileptic drug studies; Intraoperative Electrocorticography; Intraoperative and Extraoperative Functional mapping of cortex; Intracarotid Amytal tests; General Neurology on W8B.