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@article{Nutma:2019:brain/awz287,
author = {Nutma, E and Stephenson, JA and Gorter, RP and de, Bruin J and Boucherie, DM and Donat, CK and Breur, M and van, der Valk P and Matthews, P and Owen, D and Amor, S},
doi = {brain/awz287},
journal = {Brain},
pages = {3440--3455},
title = {A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis},
url = {http://dx.doi.org/10.1093/brain/awz287},
volume = {142},
year = {2019}
}

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TY  - JOUR
AB  - The 18kDa  translocator  protein  (TSPO)  is  increasingly  used  to  study  brain  and  spinal  cord  inflammation in degenerative diseases of the CNS such as multiple sclerosis. The enhanced TSPO PET  signal  that  arises  during  disease  is  widely-considered  to reflect activated  pathogenicmicroglia, although quantitative neuropathological data to support this interpretation has not been available. With the increasing  interest  in  the  role  of  chronic  microglial  activation  in  multiple  sclerosis, characterising the cellular neuropathology associated with TSPO expression is of clear importance for understanding the cellular and pathological processes on which TSPO PET imaging is reporting.Here we have studied the cellular expression of TSPO and specific binding of two TSPO targeting radioligands  ([3H]PK11195  and  [3H]PBR28)  in  tissue  sections  from  42  multiple  sclerosis  cases and  12  age-matched  controls.  Markers  of  homeostatic  and  reactive  microglia,  astrocytes,  and  lymphocytes were  used  to  investigate  the  phenotypes  of  cells  expressing  TSPO.  There  was  an  approximate 20-fold increase in cells double positive for TSPO and human leukocyte antigen -DR in active lesions and in the rim of chronic active lesion, relative to normal appearing white matter. TSPO was uniformly expressed across myeloid cells irrespective of their phenotype, rather than being   preferentially   associated   with   pro-inflammatory   microglia   or   macrophages.   TSPO+astrocytes were increased up to 7-fold compared to normal appearing white matter across all lesion sub-types  and  accounted  for  25%  of  the  TSPO+  cells  in  these  lesions.  To  relate  TSPO  protein  expression to ligand binding, specific binding of the TSPO ligands [3H]PK11195 and [3H]PBR28was determined in the same lesions. TSPO radioligand binding was increased up to seven times for [3H]PBR28 and up to two times for [3H]PK11195 in active lesions and the centre of chronic ac
AU  - Nutma,E
AU  - Stephenson,JA
AU  - Gorter,RP
AU  - de,Bruin J
AU  - Boucherie,DM
AU  - Donat,CK
AU  - Breur,M
AU  - van,der Valk P
AU  - Matthews,P
AU  - Owen,D
AU  - Amor,S
DO  - brain/awz287
EP  - 3455
PY  - 2019///
SN  - 1460-2156
SP  - 3440
TI  - A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis
T2  - Brain
UR  - http://dx.doi.org/10.1093/brain/awz287
UR  - http://hdl.handle.net/10044/1/72546
VL  - 142
ER  -

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