Quantitative autoradiographic localization of binding sites to excitatory and inhibitory receptors in epileptic-damaged hippocampus

Abnormalities within different transmitter systems may contribute to the brain damage seen in epilepsy and to the epileptogenesis. In order to elucidate the distribution of excitatory and inhibitory transmitter receptors, quantitative receptor autoradiography was performed in human hippocampi (n = 9) resected at surgery for temporal lobe epilepsy (TLE) and in nonepileptic autopsy controls (n = 6). Tissue pathology was studied in parallel to evaluate the relationship between receptor densities and neuronal loss. The binding to the excitatory N-methyl-d-aspartate (NMDA) receptor/channel site and to the muscarinic cholinergic receptor was measured. Inhibitory receptors chosen for study were the γ-aminobutyric acid type A (GABA_A) and benzodiazepine (BZ). There was a strong correlation between reduced receptor binding and neuronal loss. A general reduction in binding to all receptors was seen in epileptic patients compared to controls, most pronounced in the cornu ammonis (CA) 1, the area with most severe sclerosis. There was a greater relative reduction in binding to excitatory receptors than to inhibitory receptors. NMDA/channel receptor binding was reduced between 68% and 98% and muscarinic receptor binding between 32% and 75% in different hippocampal regions. The corresponding reduction to GABA_A receptors was 3%–65% and to BZ receptors 0%–81%. These data may support the theory that brain damage seen in TLE is caused by excessive excitatory activation.