scholarly journals Experimental autoimmune encephalomyelitis (EAE) course in prenatally stressed rat males, the offspring of mothers with different sensitivity to EAE

2019 ◽  
Vol 24 ◽  
pp. 244-248
Author(s):  
S. V. Utevska
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Sex Hormones ◽  
Prenatal Stress ◽  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Clinical Scores ◽  
Prenatally Stressed ◽  
Experimental Autoimmune

Aim. The research is aimed at investigating the effect of prenatal stress on the incidence and course of experimental autoimmune encephalomyelitis (EAE) as well as the level of sex hormones in 200-days-old male rats, offspring of females with different sensitivity to EAE induction. Methods. The incidence and severity of EAE including duration of latent period, duration of the period from the first to the maximum manifestation of motor disfunction, mean clinical scores, maximum level of motor disfunction (maximum clinical scores) were analyzed in rats with induced EAE. Serum testosterone, estradiol and progesterone levels were measure during Enzyme-Linked Immunosorbent Assay (ELISA). Results. The estradiol level of prenatally stressed males was significantly lower than in rats from the control group. Sensitive to EAE test male rats had lower testosterone levels than EAE resistant males, and the offspring of EAE sensitive mothers were more resistant to EAE induction than the offspring of EAE resistant mothers. Conclusions. Without significant changes in the course of EAE, the reduction in incidence depends on a combination of factors such as mother's sensitivity to EAE induction and prenatal stress. Keywords: experimental autoimmune encephalomyelitis (EAE), prenatal stress, sex hormones, sensitivity to EAE induction.

scholarly journals Prenatal stress-induced sex differences in the incidence and course of experimental autoimmune encephalomyelitis in rats

2018 ◽  
Vol 23 ◽  
pp. 238-243
Author(s):  
S. V. Utevska ◽  
V. V. Geyko
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Neurological Deficit ◽  
Prenatal Stress ◽  
Maximum Level ◽  
Autoimmune Encephalomyelitis ◽  
Offspring Sex ◽  
Prenatally Stressed ◽  
Old Rats ◽  
Old Females ◽  
Experimental Autoimmune

Aim. The research is aimed at investigating the effect of prenatal stress on the incidence and course of experimental autoimmune encephalomyelitis (EAE) in four-month-old rats, offspring of females with different sensitivity to EAE induction. Methods. The incidence and severity of EAE (duration of latent period (LP)), the maximum level of neurological deficit (KSmax) and the duration of the period from the first to the maximum manifestations of neurological deficit (T)) were analyzed in rats with induced EAE. Results. A decrease in the incidence of EAE in prenatally stressed four-month-old females, whose mothers were sensitive to induction of EAE, was found. Differences in the dynamics of EAE course in males from the control and prenatally stressed group were revealed. Conclusions.The EAE incidence and EAE course traits in four-month-old rats depend on a complex of factors: mother's sensitivity to induction of EAE, prenatal stress and offspring sex. Keywords: experimental autoimmune encephalomyelitis, prenatal stress, sex, sensitivity to induction of EAE.  

scholarly journals NAD+ attenuates experimental autoimmune encephalomyelitis through induction of CD11b+ gr-1+ myeloid-derived suppressor cells

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Jin-Li Wang ◽  
Bin Li ◽  
Guo-Jun Tan ◽  
Xiao-Li Gai ◽  
Jun-Na Xing ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Western Blot ◽  
Suppressor Cells ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Myeloid Derived Suppressor Cells ◽  
Autoimmune Encephalomyelitis ◽  
Arginase 1 ◽  
Clinical Scores ◽  
Experimental Autoimmune

Abstract Objective: To investigate the effects of nicotinamide adenine dinucleotide (NAD+) on the pathogenesis of the animal model for multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE). Methods: EAE model was induced by myelin oligodendrocyte protein (MOG 35-55). Clinical scores of EAE were measured in mice with or without NAD+ treatment. Hematoxylin and Eosin (HE) and Luxol Fast Blue (LFB) staining were performed to assess inflammation and demyelination, respectively. Expressions of target proteins were measured by Western blot. The numbers of myeloid-derived suppressor cells (MDSCs) were measured by immunofluorescent staining and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expressions of inflammatory cytokine in serum. Results: NAD+ treatment could decrease inflammatory cells and demyelination foci, attenuate the clinical scores of EAE and slightly delay disease onset. Western blot showed that NAD+ treatment up-regulated the expression of phosphorylated-STAT6 (p-STAT6) and SIRT1. Besides, NAD+ treatment up-regulated the expression of p-IκB and down-regulated the expression of p-NF-κB. In addition, NAD+ treatment could increase the numbers of CD11b+ gr-1+ MDSCs and the expression of Arginase-1. Moreover, NAD+ treatment up-regulated the expressions of IL-13 and down-regulated the expression of IFN-γ and IL-17. Conclusions: The present study demonstrated that NAD+ treatment may induce the CD11b+ gr-1+ MDSCs to attenuate EAE via activating the phosphorylation of STAT6 expression. Therefore, NAD+ should be considered as a potential novel therapeutic strategy for MS.

The Effects of D-aspartate on Neurosteroids, Neurosteroid Receptors, and Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 19 (3) ◽  
pp. 316-325
Author(s):  
Mahdi Goudarzvand ◽  
Yaser Panahi ◽  
Reza Yazdani ◽  
Hosein Miladi ◽  
Saeed Tahmasebi ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Mediators ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Gavage ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
17Β Estradiol ◽  
The Brain ◽  
Experimental Autoimmune

Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice. Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits. Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice. Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage.

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 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.

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

2021 ◽  
Author(s):  
Yasaman Honarmandnasab ◽  
Mohammad Reza Kordi ◽  
Abbas Ali Gaeini
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Wheel Running ◽  
Clinical Score ◽  
Exercise Group ◽  
Voluntary Exercise ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Healthy Control ◽  
And Control ◽  
Experimental Autoimmune

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.

scholarly journals Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling

2020 ◽  
Vol 11 ◽  
Author(s):  
Ye Yu ◽  
Dong-Ming Wu ◽  
Jing Li ◽  
Shi-Hua Deng ◽  
Teng Liu ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intragastric Administration ◽  
Autoimmune Encephalomyelitis ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory ◽  
Inflammasome Activity ◽  
Experimental Autoimmune

Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by demyelination and chronic neuroinflammation. Bixin is a carotenoid isolated from the seeds of Bixa orellana that exhibits various potent pharmacological activities, including antioxidant, anti-inflammatory, and anti-tumor properties. However, the effects of bixin on MS have not yet been examined. To evaluate the effects and underlying molecular mechanisms of bixin on MS, experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated via intragastric administration of bixin solutions. To evaluate the molecular mechanisms of bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay analyses were performed. We found that bixin significantly improved the symptoms and pathology in EAE mice, reduced the release of inflammatory cytokines TNF-α, IL-6, IL-8, IL-17, and IFN-γ, and increased the expression of the anti-inflammatory cytokine IL-10. And bixin reduced the proportion of Th1 and Th17 cells in the spleen and CNS, and suppressed microglia aggregation, and TXNIP/NLRP3 inflammasome activity by scavenging excessive reactive oxygen species (ROS) in EAE mice. Furthermore, bixin inhibited inflammation and oxidative stress via activating nuclear factor erythroid 2-related factor 2 (NRF2), and its downstream genes in EAE mice, meanwhile, these effects were suppressed upon treatment with an NRF2 inhibitor, ML385. Bixin prevented neuroinflammation and demyelination in EAE mice primarily by scavenging ROS through activation of the NRF2 signaling pathway. Taken together, our results indicate that bixin is a promising therapeutic candidate for treatment of MS.

scholarly journals Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes

2021 ◽  
Author(s):  
Yue Lang ◽  
Fengna Chu ◽  
Lingling Liu ◽  
Chao Zheng ◽  
Chunrong Li ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Nlrp3 Inflammasome ◽  
Demyelinating Disease ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Treatment Groups ◽  
Prevention And Treatment ◽  
Nlrp3 Inflammasomes ◽  
Experimental Autoimmune

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.

scholarly journals Regular Exercise Training Enhances Spatial Memory and Regulates Glucocorticoid System in Experimental Autoimmune Encephalomyelitis

2021 ◽  
Author(s):  
Muthanna Hafedh ◽  
Abdolhossein Parnow ◽  
Cyrus Jalili ◽  
Darpan I. Patel
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Spatial Memory ◽  
Repeated Measures ◽  
Water Maze ◽  
Clinical Score ◽  
Enzyme Linked Immunosorbent Assay ◽  
Regular Exercise ◽  
Autoimmune Encephalomyelitis ◽  
Post Hoc ◽  
Experimental Autoimmune

Abstract Background & objective: Exercise has been show to improve cognitive function in patients with multiple sclerosis (MS). Experimentally, glucocorticoids (GCs) treatment has been observed to improve cognitive deterioration in an autoimmune model for MS, experimental autoimmune encephalomyelitis (EAE).We aimed to determine the combined effect of exercise and 4 mg/kg of dexamethasone (Dex) for 4 weeks on spatial memory in EAE.Materials & Methods: Rats with EAE were subjected to the Morris water maze (MWM) for four days and a prop test for one day. The prop test was repeated on day 40 post-induction (dpi).Rats were randomly assigned to one of four groups (10 rats per group): control EAE without treatment; EAE + dexamethasone, (EAE + Dex); EAE + exercise (EAE + Ex); and EAE+Dex+Ex . Rats receiving dexamethasone were administered 4 mg/kg injections daily for two weeks after EAE induction. We initiated exercise on a motorized treadmill 2 weeks before EAE induction and continued until 14 dpi. On day 41 animals were dissected and CORT level was assessed by enzyme-linked immunosorbent assay corticosterone kit. One-way analysis of variance (ANOVA) with repeated measures followed by a protected LSD post hoc test.Results: indicated that, EAE+Ex group increased body weight (P < 0.001) and it displayed a significantly lower CORT concentration (P <0.001) with delayed the clinical score until day 13dpi. Further EAE+Ex improved memory by time spent (p > 0.001) and swimming speed (p>0.002).Conclusions : The protocol selected in this study was as effective treatment for the EAE model to improve spatial memory and regulate corticosterone concentrations.

scholarly journals S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 22 (24) ◽  
pp. 13558
Author(s):  
Chiara Camponeschi ◽  
Maria De Carluccio ◽  
Susanna Amadio ◽  
Maria Elisabetta Clementi ◽  
Beatrice Sampaolese ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Disease Onset ◽  
Treated Group ◽  
S100b Protein ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune Encephalomyelitis Mouse ◽  
Clinical Scores ◽  
Experimental Autoimmune

S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.

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