THE ROLE OF NEURAL STEM CELLS IN THE DEVELOPMENT OF HUMAN EPILEPSY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this proposal is to determine the role of active neural stem cell (NSC) proliferation in development of recurrent seizures and neurological, cognitive, and behavioral impairments in patients following a prolonged seizure. Seizure is one of the most common neurological disorders. A substantial number of patients who experience a seizure demonstrate progressively increased seizure frequency, and nearly half of all patients eventually develop epilepsy, a pathological condition of spontaneous recurring seizures despite optimal medical therapy. Patients with epilepsy often experience significant neuropsychological impairments, affecting their learning, job opportunities, and quality of life. This is particularly evident in childhood onset epilepsy. Despite extensive research, the biological mechanisms that lead to long-term alterations in cognition and sometimes progression to medically intractable seizures are still poorly understood. The most common site for the development of severe intractable epilepsy is located in the temporal lobe. Several studies in animal models of temporal lobe epilepsy have revealed significant activation of NSC within 3-7 days after a prolonged convulsive seizure. This process could not be studied in patients with epilepsy as, up to now, there have been no reliable biological markers to trace the fate of human NSC in vivo. Recently, a metabolic biomarker of NSC has been identified by Dr. Savatic, which enables us to investigate, for the first time, the fate of NSC in the human brain after a seizure, using noninvasive, high-resolution proton Magnetic Resonance Spectroscopy (1HMRS).