Quantitative evaluation of central-type benzodiazepine receptors with [(125)I]Iomazenil in experimental epileptogenesis: II. The rat cortical dysplasia model

Abstract

[(123)I]Iomazenil (IMZ) is a specific ligand for central-type benzodiazepine receptors (BZRs) and is available for single photon emission computed tomography (SPECT) to detect epileptogenic foci. We have recently demonstrated time-dependent alterations of [(125)I]IMZ binding in the rat kainate model of temporal lobe epilepsy. Quantitative evaluation of central-type benzodiazepine receptors with [(125)I]Iomazenil in experimental epileptogenesis. I. The rat kainate model of temporal lobe epilepsy. In the present study, we investigated regional changes in central-type BZRs in the cortical dysplasia (CD) model of epilepsy in rats. Pregnant rats were irradiated at day 17 of gestation with 1.2 Gy to produce CD in their pups, and in vitro autoradiography with [(125)I]IMZ was performed at 8 weeks after birth. Intact rats at the same age were used as controls. [(125)I]IMZ binding was significantly decreased in various cortical regions of the in utero irradiated rats, including the bilateral frontal cortex (down to 92-93% of control), cingulate cortex (91-92%), hippocampal areas CA1 (95%), CA2 (94-95%) and CA4 (95-96%), and caudate/putamen (90-94%). In addition, amygdala-kindling was significantly facilitated in the CD model, especially during the late phase of kindling, suggesting seizure susceptibility of this model. These results may replicate the clinical usefulness of central-type BZRs neuroimaging for detection of human epileptogenic CD and indicate dysfunction of GABA-A/BZR-mediated inhibition responsible for the seizure susceptibility.