scholarly journals Effect of Voluntary Training after the Induction of Experimental Autoimmune Encephalomyelitis on Some Myelin-Producing Proteins in Female C57BL/6 Mice

Author(s):  
Yasaman Honarmandnasab ◽  
Mohammad Reza Kordi ◽  
Abbas Ali Gaeini

Introduction: The aim of the present study was to investigate the effect of voluntary training period after the induction of experimental autoimmune encephalomyelitis (EAE) on some myelin-producing proteins in C57BL/6 female mice. Methods: In this experimental study first 28 mice, which were 6-8 weeks old, were purchased and were randomly divided into three groups. Exercise activity (n=12), healthy control (n=8) and experimental autoimmune encephalomyelitis (EAE) control (n=8). Voluntary exercise group did exercises, 1 hour, 5 days a week for 4 weeks after induction of EAE and having the clinical score one for two days in a row. 48 hours after final exercise section, the mice were killed and immunohistochemistry was used to evaluate the expression of MBP and CNPase proteins. Using SPSS version 16 software, multiple analysis of variance and LSD post hoc test were used to examine the groups' data differences. Results: The results showed that the expression of both proteins as a result of voluntary exercise had a significant increase in the exercise group compared to the EAE control group ( p<0.05).( in White Matter: MBP, Wheel Running and Control EAE, P= .017; Wheel Running and Healthy Control, P= .001; CNPase, Wheel Running and Control EAE, P= .015; Wheel Running and Healthy Control, P= .000; in Gray Matter: MBP, Wheel Running and Control EAE, P= .000; Wheel Running and Healthy Control, P= .000; CNPase, Wheel Running and Control EAE, P= .005; Wheel Running and Healthy Control, P= .001. Conclusion: Voluntary exercise may have a positive effect on increasing myelination in treatment and control of MS.

2020 ◽  
Author(s):  
Zahra Navi ◽  
Mozhdeh Jafari Rad ◽  
Abdolmajid Fata ◽  
Elham Moghaddas ◽  
Mahmoud Mahmoudi ◽  
...  

Abstract Background Experimental Autoimmune Encephalomyelitis (EAE) is an animal model of Multiple Sclerosis (MS). This study was conducted to evaluate the efficacy of Dicrocoelium ova on Experimental Autoimmune Encephalomyelitis (EAE) treatment in C57BL6 mice.Methods Twenty-eight C57BL/6 mice were assigned in four groups as control(C), prophylaxis (P), treatment1 (T1), and treatment2 (T2). Prior to induction of EAE in prophylaxis group and on days 7 and 18 in T1 and T2 groups, respectively, Dicrocoelium eggs were injected to each mouse. Clinical score, weight changes, and incidence time of EAE were recorded. IFN- γ and IL-4 assay and histopathological study by (H&E) and Toluidine-Blue (TB), and Luxol Fast Blue (LFB) were done. Data were analyzed using SPSS software version 21.Results The disease score was significantly lower in P and T1 groups than the control group (p=0.01). IFN- γ was lower in P and T1 groups than the control group. The highest level of IL-4 was observed in the T1 group. The total number of Neuroglia cells of corpus callosum was similar in all groups, but density increased in T1 group compared to the control group (P = 0.03).Conclusions : The results of the study showed that, Dicrocoelium eggs have the great potential efficacy to stimulate immunomodulation toward treatment of EAE during the initial phase.


2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Maiara Carolina Perussolo ◽  
Bassam Felipe Mogharbel ◽  
Lucia de Noronha ◽  
Katherine Athayde Teixeira de Carvalho

Abstract Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized as an inflammatory demyelinating disease. It presents a diversity of neurologic signs and symptoms as well the incapacities. Since the need for advances in MS treatment, many studies are for new therapeutic technologies, mainly through using preclinical models as experimental autoimmune encephalomyelitis (EAE). This study aimed to observe and analyze the development in Lewis rats-induced model of EAE. Methods It was used 23 females of Rattus norvegicus, from 6 to 8 weeks, weighing around 170 g. Of 23 rats, 19 underwent EAE induction distributed in six groups to establish the evolution of clinical signs. B. pertussis toxin (PTX) doses were 200, 250, 300, 350–400 ng, and four animals as the control group. The animals had weight and scores analyzed daily, starting seven and ending 24 days after induction. Then, all animals were euthanized, and the brain and spinal cord were collected for histopathological analyses. Results The results showed that the dose of 250 ng of PTX induced de higher score and weight reduction. All groups who received the PTX demonstrated histopathological findings. Those characterized as leukocyte infiltration, activation of microglia and astrocytes, and demyelinated plaques in the brain. In the spinal cord, the loosening of the myelinated fibers was observed by increasing the axonal space in all tested doses of PTX. Conclusions EAE was not dose-dependent. Histopathological findings do not proportionally related to clinical signs, as in human patients with MS.


Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 748 ◽  
Author(s):  
Gabriele Di Sante ◽  
Susanna Amadio ◽  
Beatrice Sampaolese ◽  
Maria Elisabetta Clementi ◽  
Mariagrazia Valentini ◽  
...  

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellular signaling molecule. A direct correlation between increased amount of S100B and demyelination and inflammatory processes has been demonstrated. The aim of this study is to investigate the possible role of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of disease progression in the relapsing–remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the central nervous system, we observed that pentamidine is able to delay the acute phase of the disease and to inhibit remission, resulting in an amelioration of clinical score when compared with untreated relapsing–remitting experimental autoimmune encephalomyelitis mice. Moreover, we observed a significant reduction of proinflammatory cytokines expression levels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxide synthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modify the neuropathology of the disease, reducing immune infiltrates and partially protecting the brain from the damage. Overall, our results indicate that pentamidine targeting the S100B protein is a novel potential drug to be considered for multiple sclerosis treatment.


Author(s):  
Seyed Abdollah Samani ◽  
◽  
Mohamad Raman Moloudi ◽  
Rashid Ramezan Zadeh ◽  
Mohammad Abdi ◽  
...  

Introduction: Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. In this study, the potential of Enterococcus durans and three various strains of lactobacilli (lacto-mix), Including L.rhamnosus, L.casei, and L.plantarum for prevention of Experimental Autoimmune Encephalomyelitis (EAE) features were evaluated. Methods: C57BL/6 female mice were inoculated with (MOG35-55) / (CFA) to induce EAE. Different groups (five groups: n = 6 in each group) of animals received saline or probiotics by oral gavage with 200 µl of lactobacilli (1.5 *108 CFU/ml) for 2 week before the immunization and during the test for one month. Results: Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in the probiotic-treated animals. Pro-inflammatory cytokines (IL-17 and IFN-g) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (p <0.01), while in the spinal cord tissue there was a decrease in IL-17 in those animals treated with the Lacto-mix and Edu + Lacto- mix (p <0.01) and a significant decrease in IFN-g in those animals that received Edu (p <0.05). Western blot analysis of MMP-9 and MBP proteins showed a decrease and increase in treatment and EAE groups, compared to the normal control group respectively. Conclusion: our data suggest that probiotic Enterococcus durans and lacto-mix had a preventive effect against EAE but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials.


1994 ◽  
Vol 77 (5) ◽  
pp. 2341-2347 ◽  
Author(s):  
C. Le Page ◽  
A. Ferry ◽  
M. Rieu

We examined whether physical exercise affected the development of an autoimmune response, experimental autoimmune encephalomyelitis (EAE), which is a demyelinating disease leading to paralysis. EAE was inducted on day 0, in rats of both sexes, by injecting them with spinal cord tissue in adjuvant. From days 1 to 10 after injection, exercised rats (n = 55) ran on a treadmill (60–120 min/day) before the onset of the paralytic disease. Clinical signs of the disease (ataxia, paralysis, and body mass loss) were examined in exercised and control rats (n = 54). Three types of EAE were induced: monophasic, acute, and chronic relapsing (CR)-EAE (3 bouts of disease, CR-EAE 1, 2, and 3, separated by remissions). Exercise significantly delayed the onset of CR-EAE 1 (P = 0.001) and the 1st day of maximum severity of CR-EAE 1 (P = 0.001) and CR-EAE 2 (P = 0.002). Moreover, the duration of CR-EAE 1 was significantly decreased in exercised rats compared with control rats (P = 0.004). The peak severity of the different types of EAE was not modified by exercise. The present study indicates that endurance exercise during the phase of induction of EAE diminished lightly only one type of EAE (CR-EAE) and therefore did not exacerbate the autoimmune disease.


Pain ◽  
2019 ◽  
Vol 160 (4) ◽  
pp. 870-881 ◽  
Author(s):  
Katherine A. Mifflin ◽  
Muhammad S. Yousuf ◽  
Kevin C. Thorburn ◽  
Jennifer. Huang ◽  
Maria Elisa Pérez-Muñoz ◽  
...  

2013 ◽  
Vol 38 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Darpan I. Patel ◽  
Lesley J. White

The impact of exercise on disease progression in multiple sclerosis (MS) is unclear. In the present study, we evaluated the clinical effects of forced wheel running on rats induced with experimental autoimmune encephalomyelitis (EAE), a model of MS. Female Lewis rats (n = 40) were randomly assigned to 1 of 4 groups prior to inoculation: EAE exercise (EAE-Ex), EAE sedentary (EAE-Sed), control exercise (Con-Ex), or control sedentary (Con-Sed). Exercise training was composed of forced treadmill running at increasing intensity across 10 consecutive days. No significant differences in clinical disability were observed in the EAE groups at the conclusion of this study. Furthermore, no significant differences in brain mass were observed across groups. Analysis of brain tissue proteins revealed that tumour necrosis factor-α (TNF-α) concentrations were higher in both EAE groups compared with the control groups (p < 0.05); however, no significant differences were seen between the EAE-Ex and EAE-Sed groups. The Con-Ex group had lower whole-brain TNF-α compared with the Con-Sed group (p < 0.05). Nerve growth factor concentrations were greater in the EAE-Ex animals compared with both control groups (p < 0.05 for both). No differences were seen in brain-derived neurotrophic factor. Our results indicate that aerobic exercise can modulate the proteins associated with disability in EAE; however, further research is required to understand the total impact of exercise on EAE disability and disease progression.


2016 ◽  
Vol 50 (6) ◽  
pp. 427-432 ◽  
Author(s):  
Pushpalatha Palle ◽  
Filipa M Ferreira ◽  
Axel Methner ◽  
Thorsten Buch

Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants. Varying scales with differing parameters are used and thus limit comparability of experiments. Incorrect use of statistical analysis tools to assess EAE data is commonplace. In experimental practice the clinical score is used not only as an experimental readout, but also as a parameter to determine animal welfare actions. Often overlooked factors such as the animal’s ability to sense its compromised motoric abilities, drastic though transient weight loss, and also the possibility of neuropathic pain, make the assessment of severity a difficult task and pose a problem for experimental refinement.


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.


Author(s):  
Yue Lang ◽  
Fengna Chu ◽  
Lingling Liu ◽  
Chao Zheng ◽  
Chunrong Li ◽  
...  

Abstract Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system. NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, is implicated in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which NLRP3 inflammasome is involved in the development of MS and EAE is not clear. NF-kappaB (NF-κB) is associated with the activity of NLRP3 inflammasomes, but the role of NF-κB is controversial. We sought to demonstrate that both NF-κB and NLRP3 contribute to development of MS and EAE, and NF-κB pathway is positively correlated with NLRP3 activation in EAE. The inhibitor of NF-κB and NLRP3, BAY11-7082, can prevent and treat EAE. BAY11-7082 (5mg/kg/i.p and 20 mg/kg/i.p) was intraperitoneally administered to EAE mice at the time of second injection of pertussis toxin (BAY11-7082 prevention group) or at the onset of symptoms (BAY11-7082 treatment group). mRNA expressions of NLRP3 were determined by qPCR. Protein expressions of NLRP3, NF-κBp65, and phosphorylated-p65 were determined by Western blotting. Serum levels of inflammatory cytokines were measured by Cytometric Bead Array. Mice treated with BAY11-7082 (both prevention and treatment groups) showed lower clinical scores and attenuated pathological changes. NLRP3 inflammasome and activity of NF-κB in spinal cord of EAE mice was higher than that in control group. However, the level of NLRP3 inflammasome decreased in BAY11-7082 prevention and treatment groups. BAY11-7082 is a promising therapeutic agent for MS. NLRP3 activation in EAE maybe related with NF-κB pathway.


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