Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis

Author(s):  
Dalila NJ. Mancino ◽  
Analia Lima ◽  
Paulina Roig ◽  
Luis M García Segura ◽  
Alejandro F. De Nicola ◽  
...  
Author(s):  
Laura Garay ◽  
Maria Claudia Gonzalez Deniselle ◽  
Lobke Gierman ◽  
Analia Lima ◽  
Paulina Roig ◽  
...  

Abstract: Pregnant women with multiple sclerosis (MS) show disease remission in the third trimester concomitant with high circulating levels of sex steroids. Rodent experimental autoimmune encephalomyelitis (EAE) is an accepted model for MS. Previous studies have shown that monotherapy with estrogens or progesterone exert beneficial effects on EAE. The aim of the present study was to determine if estrogen and progesterone cotherapy of C57BL/6 female mice provided substantial protection from EAE.: A group of mice received single pellets of progesterone (100 mg) and 17 β-estradiol (2.5 mg) subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes.: Clinical signs of EAE were substantially attenuated by estrogen and progesterone treatment. Steroid cotherapy prevented spinal cord demyelination, infiltration of inflammatory cells and GFAP: Cotherapy with estrogen and progesterone inhibits the development of major neurochemical abnormalities and clinical signs of EAE. We suggest that a combination of neuroprotective, promyelinating and immuno-suppressive mechanisms are involved in these beneficial effects.


2019 ◽  
Vol 6 (1) ◽  
pp. 17-58 ◽  
Author(s):  
Bert A. 't Hart

Abstract. Aging Western societies are facing an increasing prevalence of chronic autoimmune-mediated inflammatory disorders (AIMIDs) for which treatments that are safe and effective are scarce. One of the main reasons for this situation is the lack of animal models, which accurately replicate clinical and pathological aspects of the human diseases. One important AIMID is the neuroinflammatory disease multiple sclerosis (MS), for which the mouse experimental autoimmune encephalomyelitis (EAE) model has been frequently used in preclinical research. Despite some successes, there is a long list of experimental treatments that have failed to reproduce promising effects observed in murine EAE models when they were tested in the clinic. This frustrating situation indicates a wide validity gap between mouse EAE and MS. This monography describes the development of an EAE model in nonhuman primates, which may help to bridge the gap.


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