The basic neurochemical mechanisms underlying the various human epilepsies are as yet unknown. Our current knowledge of the human brain in situ is extremely limited. One approach which may prove to be especially valuable is in vivo neurochemistry using intracerebral microdialysis. This method has recently been established as a means of quantifying extracellular levels of neurochemicals in specific brain regions in both anesthetized and awake, freely-moving animals. This proposal aims to extend microdialysis to use in humans and provide novel data on hippocampal neurochemistry in vivo in patients with intractable temporal lobe epilepsy (TLE). The major focus of the proposed experiments will be the role of the excitatory amino acids, glutamate and aspartate, as well as the NMDA-receptor ligands, quinolinic acid and kynurenic acid. The net balance between endogenous excitatory and inhibitory compounds will be determined by also measuring GABA, taurine, adenosine, the monoamines and the neuropeptide, somatostatin. Further information regarding metabolic activity will be determined using lactography, the on-line analysis of extracellular lactate. Measurements of the cyclic nucleotide, cAMP may suggest alterations in the number and/or function of adenylate cyclase-coupled receptors and levels of extracellular Ca++ will also be determined on-line. The association between electrophysiological and neurochemical events will be determined by simultaneous EEG monitoring using depth electrodes . A profile of in vivo neurochemistry will be generated with the emergence of inhibitory/excitatory patterns specific to TLE. In addition, dynamic data obtained via either on-line or with rapid time resolution will help determine the neurochemical substrates of seizure generation, spread and arrest. Such data will be used both to develop new treatment strategies, and as a way of focusing further cellular and molecular biological approaches to epilepsy.
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