Neurotransmitter, receptor and biochemical changes in monkey cortical epileptic foci

Abstract

Epileptic and normal Macaca mulatta monkey cortex was investigated using ligand binding techniques. Subpial injections of aluminum hydroxide gel into the left sensorimotor cortex produced stable seizure frequencies over a two year period and resulted in specific biochemical and receptor abnormalities. Pair matched CSF samples comparing epileptic and non-epileptic hemispheres showed a significant decreased GABA concentration over the epileptic side. The epileptic cortex demonstrated markedly reduced GABA receptor binding and diminished tissue GABA concentration and GAD activity. Two patterns of receptor loss were observed: nonspecific local cellular drop out involving multiple neurotransmitter receptors; and distal receptor loss which was specific for the neurotransmitter intervention pattern of the cortex. GABAergic receptor loss was more marked than receptor losses for the other neurotransmitter and was more widespread. Scatchard plot analysis demonstrated that the diminished GABAergic receptors within the focus were due to receptor loss and not affinity changes. Spearman rank correlations showed a significant correlation only between the degree of GABAergic receptor loss or decrease in GAD activity and the seizure frequency. Epilepsy appears to be a multifactoral disorder with multiple neuroreceptor abnormalities, the most notable of which are the destruction of GABAergic neurons and GABA receptors.