Epilepsy

Several findings suggest that energy metabolism and the glutamate-glutamine cycle may be impaired in epilepsy. Positron emission tomography often shows interictal hypometabolism of the epileptogenic hippocampus. In vivo microdialysis studies show that seizure-associated glutamate release is doubled and clearance is slowed. We hypothesized that the glutamate-glutamine cycle between neurons and glia may be decreased in the epileptic human hippocampus.

We are measuring the ratio of the glutamate-glutamine cycle to the neuronal tricarboxylic acid cycle (TCA) cycle and total glutamine synthesis in the interictal, epileptogenic hippocampus of patients with medically refractory mesial temporal lobe epilepsy. Defects in the glutamate-glutamine cycle could reflect mitochondrial dysfunction in neuron or glia or both. We propose to determine whether there is such a defect and correlate it with presurgical in vivo measurements, histochemical measurements, and functional measurements.

The effects of antiepileptic drugs on brain gamma-aminobutyric acid (GABA), glutamate, glutamine concentrations and glutamate/glutamine cycle are studied in a rat model using proton magnetic resonance spectroscopy (MRS) of perchloric acid extracts.

The effects of antiepileptic drugs on GABA, glutamate and glutamine concentrations and glutamate/glutamine cycle are studied in human and rat perfused, neocortical slice preparations.

Researchers :
Ognen A. C. Petroff
Douglas L. Rothman
Robin A. de Graaf
Laura D. Errante
Dennis D. Spencer
Jung H. Kim