CENTRAL BENZODIAZEPINE RECEPTOR AUTORADIOGRAPHY IN HIPPOCAMPAL SCLEROSIS

1 The gamma-aminobutyric acid (GABA)(A)/central benzodiazepine recepto r (cBZR) complex is a major inhibitory receptor in the vertebrate CNS. Binding of [C-11]-flumazenil to this complex in vivo is reduced in hi ppocampal sclerosis (HS). It has been uncertain whether reduced cBZR b inding is entirely due to neuronal loss in HS. 2 The objective of this study was to characterize abnormalities of the cBZR in HS with a corr elative autoradiographic and quantitative neuropathological study. 3 S aturation autoradiographic studies were performed with [H-3]-flumazeni l to investigate relationships between neuronal density and receptor a vailability (B-max) and affinity (K-d) in HS. Hippocampal tissue was o btained al surgery from 8 patients with intractable temporal lobe epil epsy (TLE) due to HS and autopsies of 6 neurologically normal controls . Neuronal densities were obtained by means of a 3-D counting method. 4 B-max values for [H-3]-flumazenil binding in the subiculum, CA1, CA2 , CA3, hilus and dentate gyrus were all found to be significantly redu ced in HS compared with controls and significant increases in affinity were observed in the subiculum, hilus and dentate gyrus. In HS, cBZR density in the CA1 region was significantly reduced (P<0.05) to a grea ter extent than could be attributable to neurone loss. In other region s, B-max was reduced in parallel with neuronal density. 5 In HS, there is a loss of cBZR in CA1 over and above loss of neurones. This findin g and increases in affinity for flumazenil in subiculum, hilus and den tate gyrus imply a functional abnormality of the GABA(A)/cBZR complex that may have a role in the pathophysiology of epileptogenicity in HS.