Pharmacotherapy with 17β-estradiol and progesterone prevents development of mouse experimental autoimmune encephalomyelitis

2010 ◽  
Vol 1 (1) ◽  
Author(s):  
Laura Garay ◽  
Maria Claudia Gonzalez Deniselle ◽  
Lobke Gierman ◽  
Analia Lima ◽  
Paulina Roig ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Signs ◽  
Proteolipid Protein ◽  
Inflammatory Cells ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
Mouse Experimental Autoimmune Encephalomyelitis ◽  
And Control ◽  
Experimental Autoimmune

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.

scholarly journals The induced dose of experimental autoimmune encephalomyelitis was not determinant and proportional to histopathological findings

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Maiara Carolina Perussolo ◽  
Bassam Felipe Mogharbel ◽  
Lucia de Noronha ◽  
Katherine Athayde Teixeira de Carvalho
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Histopathological Findings ◽  
The Brain ◽  
Experimental Autoimmune

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.

scholarly journals Inhalation of Dimethyl Fumarate-encapsulated solid lipid nanoparticles attenuate clinical signs of Experimental Autoimmune Encephalomyelitis and pulmonary inflammatory dysfunction in mice

2021 ◽  
Author(s):  
Bárbara Fernandes Pinto ◽  
Lorena Natasha Brito Ribeiro ◽  
Gisela Bevilacqua Rolfsen Ferreira da Silva ◽  
Camila Simões Freitas ◽  
Lucas Kraemer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Solid Lipid Nanoparticles ◽  
Clinical Signs ◽  
Dimethyl Fumarate ◽  
Lipid Nanoparticles ◽  
Oral Drug ◽  
Autoimmune Encephalomyelitis ◽  
Solid Lipid ◽  
Experimental Autoimmune

Rationale: The FDA approved Dimethyl Fumarate (DMF) as an oral drug for Multiple Sclerosis treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. Objective: Investigated the potential effects of solid lipid nanoparticles (SLN) containing DMF, administered by inhalation on the clinical signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with experimental autoimmune encephalomyelitis (EAE). Materials and Methods: EAE was induced using MOG35-55 peptide in female C57BL/6J mice and were treated via inhalation with DMF-encapsulated SLN (CTRL/SLN/DMF and EAE/SLN/DMF), empty SLN (CTRL/SLN and EAE/SLN), or saline solution (CTRL/saline and EAE/saline), every 72 hours during 21 days. Results: After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared to EAE/saline and EAE/SLN, showed decreased clinical score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3+ cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-α and IL-17, perivascular and peribronchial inflammation, with pulmonary mechanical dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. Conclusion: Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.

scholarly journals Oral Administration of Probiotic Enterococcus Durans Ameliorates Experimental Autoimmune Encephalomyelitis in Mice

2021 ◽  
Author(s):  
Seyed Abdollah Samani ◽  
◽  
Mohamad Raman Moloudi ◽  
Rashid Ramezan Zadeh ◽  
Mohammad Abdi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Control Group ◽  
Immunomodulatory Activity ◽  
Spinal Cord Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Enterococcus Durans ◽  
Experimental Autoimmune

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.

Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis

1994 ◽  
Vol 77 (5) ◽  
pp. 2341-2347 ◽  
Author(s):  
C. Le Page ◽  
A. Ferry ◽  
M. Rieu
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Autoimmune Response ◽  
Spinal Cord Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Body Mass Loss ◽  
Different Types ◽  
And Control ◽  
Experimental Autoimmune

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.

Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide

1998 ◽  
Vol 4 (3) ◽  
pp. 147-153 ◽  
Author(s):  
J D Laman ◽  
C BM Maassen ◽  
M M Schellekens ◽  
L Visser ◽  
M Kap ◽  
...  
Keyword(s):  
Spinal Cord ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Disease Burden ◽  
Proteolipid Protein ◽  
Autoimmune Encephalomyelitis ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
Cd44 Variant Isoforms ◽  
Experimental Autoimmune

Interactions between mononuclear cells are required for the formation of inflammatory infiltrates in the CNS and the activation of cellular effector functions provoking demyelination in MS. Membrane-expressed costimulatory molecules are crucial to such interactions. We therefore investigated whether two costimulatory molecules, CD40L (CD154, expressed on activated CD4-possible T cells) and selected CD44-variant isoforms (expressed on activated CD4-positive T cells), are targets for immunotherapy in MS. The model of experimental autoimmune encephalomyelitis (EAE) induced in SJL-mice by immunization with a peptide derived from the proteolipid protein (PLP139-151) was optimized to address these questions. A previous observation that anti-CD40L (CD154) monoclonal antibodies can effectively prevent EAE in this model was confirmed, and extended by demonstrating that CD40 is expressed by cells of the monocytic lineage infiltrating the spinal cord. In vivo treatment with antibody against the standard isoform of CD44 (CD44s or CD44H) did not affect disease burden. In contrast, combined treatment with antibodies against the isoforms CD44v6, v7 and v10, which are thought to be involved in inflammatory processes, reduced the disease burden considerably. In addition, CD44v10- expressing cells were detected in the spinal cord. These data support the idea that CD40-CD40L interactions form a target for immunotherapy of MS, and indicate that cells expressing CD44v6, v7 and/or v10-containing isoforms have such potential as well.

Quantitative Evaluation of Leukocyte Infiltration into the Spinal Cord in a Model of Experimental Autoimmune Encephalomyelitis: Statistical-Analytical Techniques for Use in Evaluating Drugs

1998 ◽  
Vol 11 (3) ◽  
pp. 117-137 ◽  
Author(s):  
D. L. Chapman ◽  
S. M. Vroegop ◽  
L. A. Galinet ◽  
K. A. Ready ◽  
C. J. Dunn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Monoclonal Antibody ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Negative Binomial ◽  
Clinical Signs ◽  
Clinical Disease ◽  
Leukocyte Infiltration ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is considered a useful animal model for preclinical development of drugs to treat human multiple sclerosis. The relationship between clinical disease signs and leukocyte infiltration into the lower spinal cord was studied in EAE in order to assess analytical and statistical methods for evaluating drug candidates. As expected, the degree of clinical disease was correlated with the amount of leukocyte infiltration into the lower spinal cord. Additionally, we were able to distinguish patterns of clinical signs and leukocyte infiltration for classes of recurring-remitting and progressive forms of the disease. The distributions of leukocyte infiltration sites correspond to negative binomial distributions, and the parameters calculated from the respective distributions differ significantly among disease classes. We determined the sensitivity of histological measures of the leukocyte infiltration and calculated the magnitude of differences required in order to observe statistically significant changes in leukocyte infiltration. Using immunohistochemistry to assess cell surface markers of leukocytes in the lower spinal cord, we measured the infiltration of CD4+ and CD8+ lymphocytes and cells of the macrophage/microglial lineage stained with the monoclonal antibody, F4/80. Treatment with an anti-4 integrin monoclonal antibody, PS/2, served as an indicator of how we may expect to measure the effects of new pharmaceutical agents tested using our particular model of EAE. PS/2 treatment affected clinical signs of disease only when administered very early in the time course of the disease, despite a marked statistically significant decline in CD4+ cells regardless of when the PS/2 was administered. The analytical and statistical techniques applied here may be used to design efficient and sensitive assays for the evaluation of new drugs that may prove useful in the treatment of multiple sclerosis.

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