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Tibolone [(7\u03b1,17\u03b1)\u201017\u2010hydroxy\u20107\u2010methyl\u201019\u2010norpregn\u20105(10)\u2010en\u201020\u2010in\u20103\u2010one], a synthetic estrogenic compound with tissue\u2010specific actions and used for menopausal hormone therapy, shows neuroprotective and antioxidant properties both in vivo and in vitro. In the present study, we analyzed whether tibolone plays a therapeutic role in experimental autoimmune encephalomyelitis (EAE) mice, a commonly used model of MS. Female C57BL\/6\u00a0mice were induced with the myelin oligodendrocyte glycoprotein MOG<jats:sub>35\u201355<\/jats:sub> and received s.c. tibolone (0.08\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>) injection every other day from the day of induction until death on the acute phase of the disease. Reactive gliosis, Toll like receptor 4 (TLR4), high mobility group box protein 1 (HMGB1), inflammasome parameters, activated Akt levels and myelin were assessed by a real\u2010time polymerase chain reaction, immunohistochemistry, and western blot analysis. Our findings indicated that, in the EAE spinal cord, tibolone reversed the astrocytic and microglial reaction, and reduced the hyperexpression of TLR4 and HMGB1, as well as NLR family pyrin domain containing 3\u2010caspase 1\u2010interleukin\u20101\u03b2 inflammasome activation. At the same time, tibolone attenuated the Akt\/nuclear factor kappa B pathway and limited the white matter demyelination area. Estrogen receptor expression was unaltered with tibolone treatment. Clinically, tibolone improved neurological symptoms without uterine compromise. Overall, our data suggest that tibolone may serve as a promising agent for the attenuation of MS\u2010related inflammation.<\/jats:p>","DOI":"10.1111\/jne.13078","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T15:46:06Z","timestamp":1639064766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis"],"prefix":"10.1111","volume":"34","author":[{"given":"Dalila N. 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