STUDIES OF HUMAN EPILEPTIC FOCUS

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In the previous fiscal year the survey of receptors, neuropeptides, amino acids, enzymes and receptors in the epileptic focus was completed. The major findings of the project can now be summarized as follows: (1) Fodrin has been found to degrade immediately following a seizure. (2) In the human epileptic focus he amino acids aspartate, glutamate and glycine were elevated in the epileptic focus when compared to nonfocal tissue removed from the same patients. Gamma amino butyric acid was not found to be different between focus an nonfocus. (3) The peptides somatostatin and neuropeptide Y were elevated in the focus. Other peptides such as B-endorphin, corticotropin releasing factor, vasoactive intestinal peptide were not altered significantly. (4) The catecholamines dopamine, norepinephrine and dopa were all elevated in the epileptic focus. (5) The enzymes tyrosine hydroxylase and choline acetyltransferese were elevated in the epileptic focus. Glutamic acid decarboxylase and Na-K ATPase showed no significant difference. (6) The muscarinic cholinergic and adrenergic receptors lower, whereas N-methyl-D-aspartate (NMDA) receptors were higher in the epileptic focus. ( 7) Serotonin, 5-hydroxyindole acetic acid (5HIAA) were also elevated in the epileptic focus. Currently, based on the findings from the past year, the human brain will be investigated using receptor autoradiography to determine microscopic distribution of the receptors. In addition, the human brain will be investigated using fresh tissue slices to understand the interactions of receptors for NMDA, catecholamines and somatostatin, through second messenger systems. The NMDA receptor will be further investigated with respect to its components such as PCP, glycine and zinc interactions. In addition, the epileptic focus obtained from patients with intractable seizures will be screened for abnormalities in amino acid, catecholamine and neuropeptide levels. Techniques of autoradiography will also be used to study the NMDA receptor.