Brain and Cerebrospinal Fluid Quinolinic Acid Concentrations in Patients with Intractable Complex Partial Seizures
Excitatory amino acids have been implicated in development and maintenance of seizures (Anderson et al., 1987; Meldrum 1987). In accordance with this notion are the observations that antagonists of excitatory amino acid receptors, including the NMDA receptor, are potent anticonvulsants (Meldrum et al., 1988). In the widely used model of kindling, electrophysiologic studies have demonstrated an increased sensitivity of NMDA receptors at stages IV and V (Mody et al., 1988). In man, increases in the concentrations of glutamate and aspartate, but not of GABA, have been reported in the focal compared to non-focal regions of cerebral cortex (Nadi et al., 1987; Sherwin et al., 1988). Additional studies have shown an increased number of NMDA receptors in the epileptic focus (Wyler et al., 1987). Studies in experimental animals have shown that local application of quinolinic acid (QUIN) increases neuronal activity (Perkins and Stone, 1983) and may cause seizures (Lapin, 1982). Conceivably, QUIN may therefore contribute to increased neuronal excitability in human seizure disorders. Direct measures of QUIN in human epilepsy have not been reported, although decreases in the degradative enzyme of QUIN, quinolinic acid phosphoribosyltransferase (QPRT), have been published (Feldblum et al., 1988), possibly indicating an impaired ability to catabolize QUIN.
KeywordsNMDA Receptor Excitatory Amino Acid Quinolinic Acid Complex Partial Seizure Epileptic Focus
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