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Central-type Benzodiazepine Receptors and Epileptogenesis: Basic Mechanisms and Clinical Validity

  1. Kiyoshi Morimoto1,
  2. Hiroshi Tamagami2,
  3. Kazumi Matsuda3

Article first published online: 29 JUN 2005

DOI: 10.1111/j.1528-1167.2005.01030.x

Issue

Epilepsia

Epilepsia

Volume 46, Issue Supplement s5, pages 184–188, July 2005

Additional Information

How to Cite

Morimoto, K., Tamagami, H. and Matsuda, K. (2005), Central-type Benzodiazepine Receptors and Epileptogenesis: Basic Mechanisms and Clinical Validity. Epilepsia, 46: 184–188. doi: 10.1111/j.1528-1167.2005.01030.x

Author Information

  1. 1

    Department of Neuropsychiatry, Faculty of Medicine, Kagawa Medical University, Kagawa

  2. 2

    Research Center, Nihon Medi-Physics Co., Ltd., Chiba

  3. 3

    National Epilepsy Center, Shizuoka Medical Institute of Neurological Disorders, Shizuoka, Japan

*Address correspondence and reprint requests to Dr. K. Morimoto at Department of Neuropsychiatry, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793 Japan. E-mail: neuropsy@kms.ac.jp

Publication History

  1. Issue published online: 29 JUN 2005
  2. Article first published online: 29 JUN 2005

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Keywords:

  • Benzodiazepine receptor;
  • Iomazenil;
  • Kainate;
  • Kindling;
  • Cortical dysplasia;
  • Focal epilepsy;
  • SPECT

Summary: Purpose:γ-Aminobutyric acid (GABA)-A/benzodiazepine receptors (BZRs) play an important inhibitory role in epileptogenesis. [123I]Iomazenil (123I-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 123I-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 123I-IMP SPECT (for regional cerebral blood flow). We also investigated in vitro autoradiography with 123I-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 123I-IMZ and 123I-IMP SPECT. Consistent with those, marked reduction of 125I-IMZ binding was observed in hippocampal CA1-3 regions of the kainate model, which clearly paralleled pyramidal neuronal loss. In contrast, 125I-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 125I-IMZ binding in the dentate gyrus without any changes in other brain regions. In NE-CD patients, the epileptogenic foci showed decreased 123I-IMZ binding with relatively normal 123I-IMP SPECT. 125I-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.

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