Quantitative analysis of benzodiazepine receptor in temporal lobe epilepsy: [(125)I]iomazenil autoradiographic study of surgically resected specimens.
OBJECTIVE
To evaluate the changes of the inhibitory neurotransmitter receptor system related to epileptogenesis by measuring central benzodiazepine receptors (BZDRs) in surgically resected specimens of temporal lobe epilepsy by using [(125)I]iomazenil autoradiography.


METHODS
Surgically resected specimens were obtained from 66 temporal lobe epilepsy patients [51 with mesial temporal lobe epilepsy (MTLE) and 15 with non-MTLE] receiving no BZDs and seven MTLE patients receiving BZDs. BZDR densities in brain sections were measured by using [(125)I]iomazenil autoradiography. Cell densities were measured from cresyl violet-stained sections.


RESULTS
Compared with non-MTLE patients, non-BZD-treated MTLE patients showed remarkable reduction of BZDR density in the pyramidal cell region of cornu ammonis (CA) 1, CA3, and CA4, and a smaller but significant reduction in CA2 and the molecular and granule cell layers of dentate gyrus (mDG). In the MTLE group, the BZDR density in the mDG correlated with that in lateral cortex. Significant correlations between BZDR density and cell density were found in all hippocampal regions. A significant difference in BZDR density/cell-density ratio was observed in CA1 region between MTLE and non-MTLE. BZD-treated patients tended to have lower BZDR densities than did non-BZD-treated patients, although the differences did not reach significance. In all MTLE cases, [(123)I]iomazenil singlephoton emission computed tomography (SPECT) showed decreased BZDR binding in MTL.


CONCLUSIONS
In MTLE, BZDR densities decreased parallel to reduction in cell density in most hippocampal subfields, but BZDR density appeared to decrease in excess of neuron loss in CA1. [(125)I]iomazenil SPECT might be useful for detecting in vivo changes of BZDR density.
National Epilepsy Center, Shizuoka Medical Institute of Neurological Disorders, Shizuoka, Japan.
Yoshimi
Y
Sata
Kazumi
K
Matsuda
Tadahiro
T
Mihara
Masao
M
Aihara
Kazuichi
K
Yagi
Yoshiharu
Y
Yonekura
D000293:Adolescent; D000328:Adult; D001345:Autoradiography / Q000379:methods; D001569:Benzodiazepines / Q000493:pharmacokinetics / Q000627:therapeutic use; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism*; D012598:Sclerosis; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; C063038:iomazenil