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Central‐type Benzodiazepine Receptors and Epileptogenesis: Basic Mechanisms and Clinical Validity
Author(s) -
Morimoto Kiyoshi,
Tamagami Hiroshi,
Matsuda Kazumi
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2005.01030.x
Subject(s) - epileptogenesis , benzodiazepine , neuroscience , gabaa receptor , psychology , clinical neurology , medicine , receptor , epilepsy
Summary: Purpose: γ‐Aminobutyric acid (GABA)‐A/benzodiazepine receptors (BZRs) play an important inhibitory role in epileptogenesis. [ 123 I]Iomazenil ( 123 I‐IMZ) is a specific ligand for central‐type (or neuronal‐type) BNRs and is available for single‐photon emission computed tomography (SPECT) in brain disorders. We demonstrated alterations of central‐type BZRs in human focal epilepsies and their experimental models. Methods: We examined interictal 123 I‐IMZ SPECT in patients with mesial temporal lobe epilepsy (MTLE; n = 19) with hippocampal sclerosis and neocortical epilepsy with focal cortical dysplasia (NE‐CD; n = 18), and compared those with magnetic resonance imaging (MRI) and 123 I‐IMP SPECT (for regional cerebral blood flow). We also investigated in vitro autoradiography with 123 I‐IMZ at various time courses in the intraamygdala kainate, amygdala kindling, and in‐utero irradiation models. Results: In MTLE patients, the epileptogenic hippocampus often showed decreases in both 123 I‐IMZ and 123 I‐IMP SPECT. Consistent with those, marked reduction of 125 I‐IMZ binding was observed in hippocampal CA1‐3 regions of the kainate model, which clearly paralleled pyramidal neuronal loss. In contrast, 125 I‐IMZ binding was increased in the dentate gyrus at 1 month but returned to the normal level at 3–6 months, when frequent spontaneous seizures appeared. The amygdala‐kindling model demonstrated similar increases in 125 I‐IMZ binding in the dentate gyrus without any changes in other brain regions. In NE‐CD patients, the epileptogenic foci showed decreased 123 I‐IMZ binding with relatively normal 123 I‐IMP SPECT. 125 I‐IMZ binding also was decreased in the cerebral cortex, hippocampus (areas CA1, 2, and 4), and caudate/putamen of the in‐utero irradiation model. Conclusions: These results indicate that central‐type BZRs neuroimaging is useful for detection of epileptogenic foci, but their alterations differ between epilepsy subtypes and time‐courses.