Linked Life Data

11050032

Source:http://linkedlifedata.com/resource/pubmed/id/11050032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-11-17
pubmed:abstractText
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 [(11)C](R)-PK11195 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 [(3)H](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 [(3)H](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 reported as sites of pathology in multiple sclerosis. A similar pattern of [(3)H](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 cellular source of [(3)H](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 [(11)C](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expression in 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, [(11)C](R)-PK11195 PET provides a cellular marker of disease activity in vivo in the human brain.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-8950
pubmed:author
pubmed:issnType
Print
pubmed:volume
123 ( Pt 11)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2321-37
pubmed:dateRevised
2011-11-3
pubmed:meshHeading
pubmed-meshheading:11050032-Adult, pubmed-meshheading:11050032-Animals, pubmed-meshheading:11050032-Antineoplastic Agents, pubmed-meshheading:11050032-Benzodiazepines, pubmed-meshheading:11050032-Binding Sites, pubmed-meshheading:11050032-Brain, pubmed-meshheading:11050032-Carbon Radioisotopes, pubmed-meshheading:11050032-Encephalomyelitis, Autoimmune, Experimental, pubmed-meshheading:11050032-Female, pubmed-meshheading:11050032-Humans, pubmed-meshheading:11050032-Isoquinolines, pubmed-meshheading:11050032-Magnetic Resonance Imaging, pubmed-meshheading:11050032-Male, pubmed-meshheading:11050032-Microglia, pubmed-meshheading:11050032-Middle Aged, pubmed-meshheading:11050032-Multiple Sclerosis, pubmed-meshheading:11050032-Radioligand Assay, pubmed-meshheading:11050032-Rats, pubmed-meshheading:11050032-Rats, Inbred Lew, pubmed-meshheading:11050032-Tomography, Emission-Computed
pubmed:year
2000
pubmed:articleTitle
The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity.
pubmed:affiliation
MRC Cyclotron Unit and Robert Steiner Magnetic Resonance Imaging Unit, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't