QUANTITATIVE AUTORADIOGRAPHIC ANALYSIS OF IONOTROPIC GLUTAMATE-RECEPTOR SUBTYPES IN HUMAN TEMPORAL-LOBE EPILEPSY - UP-REGULATION IN REORGANIZED EPILEPTOGENIC HIPPOCAMPUS

Medically intractable temporal lobe epilepsy is a common disease typic ally associated with hippocampal damage (sclerosis) and synaptic remod elling. These changes could include increased glutamate receptor expre ssion, enhancing excitability and the potential for neuronal injury. W e directly assessed this hypothesis using quantitative in vitro recept or autoradiography to determine the densities of glutamate-, NMDA-, al pha-amino-3-hydroxy-5-methyl-isoxazoleproprionic acid (AMPA)-and kaini c acid-preferring binding sites in surgically removed hippocampi from patients with mesial temporal lobe epilepsy (sclerosis; MTLE) and pati ents with mass-associated temporal lobe epilepsy (no sclerosis; MaTLE) , compared with autopsy material. Neuronal cell counts and in situ tot al protein densities were also obtained. In general, MaTLE and autopsy binding densities were indistinguishable. In contrast, some regions o f MTLE hippocampi exhibited decreased receptor densities, with a corre sponding loss of protein. In the hilus and CA1, however, ligand bindin g densities did not differ from the comparison groups in spite of mark edly reduced protein content, consistent with increased glutamate rece ptor density. Kainate-preferring sites were distributed differently fr om the other glutamate subtypes and were uniformly decreased throughou t the MTLE hippocampus, except for a unique expression within the oute r dentate molecular layer. Along with increased NMDA and AMPA receptor densities in the hilus and CA1, this distinctive population of kainat e receptors establishes that increased glutamate receptor expression i s a feature of the remodelled MTLE hippocampus. These observations sug gest that enhanced sensitivity to glutamate may be an important elemen t in the pathophysiology of temporal lobe epilepsy.