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

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


Tiivistelmä
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.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.




Last updated on 2022-07-04 at 17:23