“Central” and “peripheral” benzodiazepine receptors

Abstract

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.

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“…In all cases, increased PTBR sites were associated with severe neuronal loss (hippocampal sclerosis) and reactive gliosis. These findings confirm and extend those of previous studies which observed increased PTBR sites in blood mononuclear cells (Caldiroli et al, 1997;Ferrarese et al, 1996;Laikin et al, 1993) and brain (Beaurain et al, 1994;Johnson et al, 1992). Novel findings in the present study are those of increased PTBR sites in material from TLE patients with hippocampal sclerosis compared to similar material from patients with no pathological evidence of hippocampal sclerosis.…”

“…Epileptic patients manifest increased binding sites for PTBR ligands in blood mononuclear cells (Caldiroli et al, 1997;Ferrarese et al, 1996;Larkin et al, 1993) as well as in brain (Beaurain et al, 1994;Johnson et al, 1992). In addition, both EL (epileptic mice; Nakamoto et al, 1996), and kainate-induced epileptic rats (Benavides et al, 1987) show increased brain densities of PTBR sites.…”

Usefulness of 123I-iomazenil SPECT for childhood focal epilepsies

“…Late IMZ-SPECT images obtained 3 hours after intravenous injection of 123 Iiomazenil reflect the distribution of central BZRs [25]. According to previous studies, the distribution of BZRs at the epileptogenic site was reduced not only in an experimental animal epilepsy model [15], but also in a resected section of the human epileptogenic tissue, which was reflected by a decrease in IMZuptake [14,26]. McDonald et al [26] showed that GABA/BZR affinity was reduced in CA1 and CA4 regions in hippocampal specimens resected from patients with intractable temporal lobe epilepsy.…”

“…It is known that BZRs are reduced in the epileptic focus [14]. Late IMZ-SPECT images obtained 3 hours after intravenous injection of 123 Iiomazenil reflect the distribution of central BZRs [25].…”

“…Many studies have reported the usefulness of interictal/ictal cerebral blood flow single photon emission computed tomography (SPECT) [8][9][10][11][12] and interictal 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) [2,3,7,10,13]. 123 I-iomazenil SPECT (IMZ-SPECT) was developed based on biochemical abnormalities existing in the epileptogenic brain lesion, and is able to detect the original epileptic focus effectively in the interictal state [14,15]. In the field of epilepsy surgery in adults, several studies have employed this procedure as a presurgical evaluation, suggesting its usefulness for accurate identification of the epileptogenic lesions [16][17][18].…”