The peripheral benzodiazepine binding site in the brain in multiple sclerosis

• DOI: 10.1093/brain/123.11.2321
• Publication Date: 2002-07-26T22:48:15Z
• Authors: R. B. Banati; J. Newcombe; R. N. Gunn; A. Cagnin; F. Turkheimer; F. Heppner; G. Price; F. Wegner; G. Giovannoni; D. H. Miller; G. D. Perkin; T. Smith; A. K. Hewson; G. Bydder; G. W. Kreutzberg; T. Jones; M. L. Cuzner; R. Myers
• Keywords: Radioligand; Encephalomyelitis

This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology. Quantitative measurements PBBS expression in vivo obtained PET and [11C](R)-PK11195 are shown to correspond animal experimental human post-mortem data on distribution pattern microglia inflammatory brain disease. Film autoradiography with [3H](R)-PK11195, a specific ligand for PBBS, showed minimal normal control CNS, whereas maximal mononuclear cells was found multiple sclerosis plaques. However, there also significantly increased [3H](R)-PK11195 outside histopathologically defined borders plaques areas, such cerebral central grey matter, that not normally reported pathology sclerosis. A similar areas containing seen animals allergic encephalomyelitis (EAE). In without identifiable focal pathology, immunocytochemical staining combined high-resolution emulsion demonstrated cellular source is microglia, which frequently retains ramified morphology. Furthermore, vitro radioligand studies confirmed microglial activation leads rise number change affinity. patients identified T1- T2-weighted MRI and, importantly, normal-appearing anatomical structures, including matter. The additional delineated neuronal projection lateral geniculate bodies history optic neuritis. summary, provides marker disease activity brain.