scholarly journals Mechanisms of DE — and Remyelination in Autoimmune Encephalomyelitis and Multiple Sclerosis

Author(s):  
Hans Lassmann ◽  
Gerda Suchanek ◽  
Mascha Schmied
2014 ◽  
Vol 275 (1-2) ◽  
pp. 136-137
Author(s):  
Rasmus Berglund ◽  
Melanie Thessen Hedreul ◽  
Roham Parsa ◽  
Petra Bergman ◽  
Maja Jagodic ◽  
...  

2000 ◽  
Vol 6 (6) ◽  
pp. 378-381 ◽  
Author(s):  
C S Constantinescu ◽  
P Freitag ◽  
L Kappos

Free radicals including peroxynitrite are induced in Multiple Sclerosis (MS). Antioxidant and peroxynitrite inhibitor uric acid (UA), suppresses the MS animal model experimental autoimmune encephalomyelitis (EAE). MS patients have lower average serum UA than controls. An inverse relationship exists between MS and gout. Glatiramer acetate (GA) suppresses EAE and is beneficial in relapsing MS. We investigated serum UA changes during open-label treatment of relapsing MS with GAA. Ten patients (six females, four males, aged 19 to 39 years, mean age 32 years) completed 6 months of GAA (Copaxone® 20 mg s.c. daily). Of these, nine completed 12 months. After 6 months on GAA, serum UA (normal, 173-359 mmol/ml for women, 258-491 mmol/ml for men) increased in nine and marginally decreased (302 to 300 mmol/ml) in a single patient. Mean UA significantly increased from 240 to 303 mol/ml (P=0.0014). At 12 months, UA remained significantly higher than at start (P=0.006) decreasing in only one patient. In contrast, we found no significant UA changes after 6 and 12 months of treatment in 21 MS patients treated with interferon b1-a (Avonex®), or in 11 treated with interferon b1-a (Rebif®), or in five placebo-treated controls. Increasing UA, a natural inhibitor of free radicals, may represent a mechanism of action of glatiramer acetate in MS.


2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.


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