Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)
Cessation of anti-VLA-4 therapy in a focal rat model of multiple sclerosis causes an increase in neuroinflammation
Julkaisun tekijät: Vainio SK, Dickens AM, Tuisku J, Eskola O, Solin O, Loyttyniemi E, Anthony DC, Rinne JO, Airas L, Haaparanta-Solin M
Kustantaja: SPRINGEROPEN
Julkaisuvuosi: 2019
Journal: EJNMMI Research
Tietokannassa oleva lehden nimi: EJNMMI RESEARCH
Lehden akronyymi: EJNMMI RES
Artikkelin numero: ARTN 38
Volyymi: 9
Julkaisunumero: 38
Sivujen määrä: 9
ISSN: 2191-219X
DOI: http://dx.doi.org/10.1186/s13550-019-0508-7
Verkko-osoite: https://ejnmmires.springeropen.com/articles/10.1186/s13550-019-0508-7
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/41097259
BackgroundPositron emission tomography (PET) can be used for in vivo evaluation of the pathology associated with multiple sclerosis. We investigated the use of longitudinal PET imaging and the 18-kDa translocator protein (TSPO) binding radioligand [F-18]GE-180 to detect changes in a chronic multiple sclerosis-like focal delayed-type hypersensitivity experimental autoimmune encephalomyelitis (fDTH-EAE) rat model during and after anti-VLA-4 monoclonal antibody (mAb) treatment. Thirty days after lesion activation, fDTH-EAE rats were treated with the anti-VLA-4 mAb (n=4) or a control mAb (n=4; 5mg/kg, every third day, subcutaneously) for 31days. Animals were imaged with [F-18]GE-180 on days 30, 44, 65, 86 and 142. Another group of animals (n=4) was used for visualisation the microglia with Iba-1 at day 44 after a 2-week treatment period.ResultsAfter a 2-week treatment period on day 44, there was a declining trend (p=0.067) in [F-18]GE-180-binding in the anti-VLA-4 mAb-treated animals versus controls. However, cessation of treatment for 4days after a 31-day treatment period increased [F-18]GE-180 binding in animals treated with anti-VLA-4 mAb compared to the control group (p=0.0003). There was no difference between the groups in TSPO binding by day 142.ConclusionsThese results demonstrated that cessation of anti-VLA-4 mAb treatment for 4days caused a transient rebound increase in neuroinflammation. This highlights the usefulness of serial TSPO imaging in the fDTH-EAE model to better understand the rebound phenomenon.
Ladattava julkaisu This is an electronic reprint of the original article. |