ro-16-0154 and Sclerosis

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Autoradiography; Benzodiazepines; Cell Count; Child; Child, Preschool; Epilepsy, Temporal Lobe; Female; Flumazenil; Hippocampus; Humans; Iodine Radioisotopes; Male; Receptors, GABA-A; Sclerosis; Temporal Lobe; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

We measured the density of two benzodiazepine (BZ) receptor subtypes in neurosurgically obtained hippocampal tissue from the seizure focus of patients with temporal lobe epilepsy (TLE) showing mesial temporal sclerosis, the most common pathologic finding in TLE. We performed quantitative in vitro receptor autoradiography with [125I]Ro 16-0154, a probe for the central-type BZ receptor and with [3H]PK 11195, a probe for the peripheral-type BZ receptor. In comparison with autopsy and neurosurgical control groups, patients with mesial temporal sclerosis had regionally selective decreased central-type and increased peripheral-type BZ receptors. These changes paralleled regional losses of neurons and proliferation of glia. Decreases of the inhibitory central-type BZ receptor may be a component of the enhanced excitability of the seizure focus and also may allow localization of the focus by in vivo neuroreceptor imaging. Single photon emission computed tomography (SPECT) imaging of two TLE patients with [123I]Ro 16-0154 suggests that this technique may provide a more sensitive means of localizing the seizure focus than current imaging methods relying on changes in blood flow or glucose metabolism.

Topics: Adult; Autoradiography; Epilepsy, Temporal Lobe; Female; Flumazenil; Hippocampus; Humans; Male; Receptors, GABA-A; Sclerosis; Tomography, Emission-Computed, Single-Photon