Abstracts

Expression of Peripheral-Type Benzodiazepine Receptors and Hippocampal Sclerosis in Human Temporal Lobe Epilepsy

Abstract number : 1.245
Submission category :
Year : 2000
Submission ID : 1402
Source : www.aesnet.org
Presentation date : 12/2/2000 12:00:00 AM
Published date : Dec 1, 2000, 06:00 AM

Authors :
Anny Sauvageau, Alain Bouthillier, C Rose, Roger F Butterworth, C H U M, Montreal, PQ, Canada.

RATIONALE:Increased binding sites for peripheral-type benzodiazepine receptors (pBZR) ligands have been described in a wide range of neurological disorders including both human and experimental epilepsy. The present study was undertaken to assess pBZR expression in relation to the degree of hippocampal sclerosis in human temporal lobe epilepsy (TLE). METHODS: CA1 to CA4 hippocampal subfields were dissected from surgical samples from patients with TLE with (n = 6) or without ( n = 3) hippocampal sclerosis and from age-matched non-epileptic (tumor) controls (n = 4). pBZR immunolabelling was assessed using a polyclonal antibody to pBZR; GFAP immunofluorescence counterstaining was used to assess the cellular localization of the pBZR changes. Receptors sites were evaluated in frozen sections using quantitative receptor autoradiography and the selective pBZR ligand 3H?-PK11195. RESULTS: Increased pBZR immunolabelling and ?3H?-PK11195 binding sites were observed in CA1??CA2, CA3, CA4 hippocampal subfields from TLE patients. The degree of immunolabelling and increased binding sites were directly correlated with the degree of reactive gliosis as revealed by GFAP immunofluorescence. CONCLUSIONS: 1. pZBR immunolabelling and binding sites for the pBZR ligand ?3H?-PK11195 are increased in hippocampi from TLE patients. 2. Increased pBZR immunolabelling was positively correlated with the degree of hippocampal sclerosis and reactive gliosis in TLE brains. 3. Activation of pBZRs is known to result in increased synthesis of neurosteroids with potent inhibitory or excitatory properties. Such changes could be implicated in the imbalance between excitation/inhibition in TLE. 4. The positron emission tomography (PET) ligand ?11C?-PK11195 could be useful in imaging hippocampal sclerosis in TLE. Funded by the Savoy Foundation and MRC Canada