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Titolo:
The peripheral benzodiazepine binding site in the brain in multiple sclerosis - Quantitative in vivo imaging of microglia as a measure of disease activity
Autore:
Banati, RB; Newcombe, J; Gunn, RN; Cagnin, A; Turkheimer, F; Heppner, F; Price, G; Wegner, F; Giovannoni, G; Miller, DH; Perkin, GD; Smith, T; Hewson, AK; Bydder, G; Kreutzberg, GW; Jones, T; Cuzner, ML; Myers, R;
Indirizzi:
Hammersmith Hosp, Imperial Coll, Sch Med, MRC,Cyclotron Unit, London W12 0NN, England Hammersmith Hosp London England W12 0NN on Unit, London W12 0NN, England Hammersmith Hosp, Imperial Coll, Sch Med, Robert Steiner Magnet Resonance Imaging Unit, London W12 0NN, England Hammersmith Hosp London England W120NN ng Unit, London W12 0NN, England Charing Cross Hosp, Imperial Coll, Sch Med, Dept Neurosci, London, EnglandCharing Cross Hosp London England h Med, Dept Neurosci, London, England Univ Coll London, Inst Neurol, Neuroinflammat Grp, London, England Univ Coll London London England ol, Neuroinflammat Grp, London, England Univ Coll London, Inst Neurol, NMR Res Unit, London, England Univ Coll London London England t Neurol, NMR Res Unit, London, England Univ Coll London, Eisai London Res Labs, London, England Univ Coll LondonLondon England Eisai London Res Labs, London, England SmithKline Beecham Pharmaceut, Dept Neurosci Res, Harlow CM19 5AD, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AD ssex, England Univ Cambridge, Dept Physiol, Cambridge CB2 1TN, England Univ Cambridge Cambridge England CB2 1TN iol, Cambridge CB2 1TN, England Karl Marx Univ, Paul Flechsig Inst Brain Res, Leipzig, Germany Karl Marx Univ Leipzig Germany lechsig Inst Brain Res, Leipzig, Germany Max Planck Inst Neurobiol, Dept Neuromorphol, Munich, Germany Max Planck Inst Neurobiol Munich Germany Neuromorphol, Munich, Germany Univ Zurich, Dept Neuropathol, CH-8006 Zurich, Switzerland Univ Zurich Zurich Switzerland CH-8006 thol, CH-8006 Zurich, Switzerland
Titolo Testata:
BRAIN
, volume: 123, anno: 2000,
parte:, 11
pagine: 2321 - 2337
SICI:
0006-8950(200011)123:<2321:TPBBSI>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GLOBAL FOREBRAIN ISCHEMIA; DISABILITY STATUS SCALE; H-3 PK11195 BINDING; ACTIVATED MICROGLIA; MAGNETIC-RESONANCE; WHITE-MATTER; PK 11195; IN-VIVO;
Keywords:
PK11195; microglia; peripheral benzodiazepine receptor; mitochondrial benzodiazepine receptor; PET; multiple sclerosis; EAE; inflammation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Banati, RB Hammersmith Hosp, Imperial Coll, Sch Med, MRC,Cyclotron Unit, Ducane Rd, London W12 0NN, England Hammersmith Hosp Ducane Rd London England W12 0NN 0NN, England
Citazione:
R.B. Banati et al., "The peripheral benzodiazepine binding site in the brain in multiple sclerosis - Quantitative in vivo imaging of microglia as a measure of disease activity", BRAIN, 123, 2000, pp. 2321-2337

Abstract

This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology. Quantitative measurements of PBBS expression in vivo obtained by PET and [C-11] are shown to correspond to animal experimental and human post-mortem data on the distribution pattern of activated microglia in inflammatory brain disease. Film autoradiography with [H-3](R)-PK11195, a specific ligand for the PBBS, showed minimal binding in normal control CNS, whereas maximal binding to mononuclear cells was found in multiple sclerosis plaques. However, there was also significantly increased [H-3](R)-PK11195 binding on activated microglia outside the histopathologically defined borders of multiple sclerosis plaques and in areas, such as the cerebral central grey matter, that are not normally reportedas sites of pathology in multiple sclerosis, A similar pattern of [H-3](R)-PK11195 binding in areas containing activated microglia was seen in the CNS of animals with experimental allergic encephalomyelitis (EAE), In areas without identifiable focal pathology, immunocytochemical staining combined with high-resolution emulsion autoradiography demonstrated that the cellularsource of [H-3](R)-PK11195 binding is activated microglia, which frequently retains a ramified morphology, Furthermore, in vitro radioligand binding studies confirmed that microglial activation leads to a rise in the number of PBBS and not a change in binding affinity. Quantitative [C-11](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expressionin areas of focal pathology identified by T-1- and T-2-weighted MRI and, importantly, also in normal-appearing anatomical structures, including cerebral central grey matter, The additional binding frequently delineated neuronal projection areas, such as the lateral geniculate bodies in patients with a history of optic neuritis, In summary, [C-11](R)-PK11195 PET provides acellular marker of disease activity in vivo in the human brain.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 19:46:44