Correlation of the onset of experimental autoimmune encephalomyelitis-like clinical signs with oedema of the spinal cord in tunicamycin-poisoned rats

1987 ◽  
Vol 78 (3) ◽  
pp. 281-294 ◽  
Author(s):  
Nicole Kerlero de Rosbo ◽  
Marjorie V. Jago ◽  
Patrick R. Carnegie ◽  
Claude C.A. Bernard
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Signs ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

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.

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.

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.

scholarly journals Axonal damage in spinal cord is associated with gray matter atrophy in sensorimotor cortex in experimental autoimmune encephalomyelitis

2019 ◽  
Vol 26 (3) ◽  
pp. 294-303 ◽  
Author(s):  
Cassandra E Meyer ◽  
Josephine L Gao ◽  
James Ying-Jie Cheng ◽  
Mandavi R Oberoi ◽  
Hadley Johnsonbaugh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gray Matter ◽  
Sensorimotor Cortex ◽  
Axonal Damage ◽  
Strongly Correlated ◽  
Autoimmune Encephalomyelitis ◽  
Normal Controls ◽  
Experimental Autoimmune

Background: Gray matter (GM) atrophy in brain is one of the best predictors of long-term disability in multiple sclerosis (MS), and recent findings have revealed that localized GM atrophy is associated with clinical disabilities. GM atrophy associated with each disability mapped to a distinct brain region, revealing a disability-specific atlas (DSA) of GM loss. Objective: To uncover the mechanisms underlying the development of localized GM atrophy. Methods: We used voxel-based morphometry (VBM) to evaluate localized GM atrophy and Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) to evaluate specific pathologies in mice with experimental autoimmune encephalomyelitis (EAE). Results: We observed extensive GM atrophy throughout the cerebral cortex, with additional foci in the thalamus and caudoputamen, in mice with EAE compared to normal controls. Next, we generated pathology-specific atlases (PSAs), voxelwise mappings of the correlation between specific pathologies and localized GM atrophy. Interestingly, axonal damage (end-bulbs and ovoids) in the spinal cord strongly correlated with GM atrophy in the sensorimotor cortex of the brain. Conclusion: The combination of VBM with CLARITY in EAE can localize GM atrophy in brain that is associated with a specific pathology in spinal cord, revealing a PSA of GM loss.

scholarly journals Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaona Acharjee ◽  
Paul M. K. Gordon ◽  
Benjamin H. Lee ◽  
Justin Read ◽  
Matthew L. Workentine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Expression Patterns ◽  
Immune Functions ◽  
Autoimmune Encephalomyelitis ◽  
Transcriptional Changes ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Experimental Autoimmune

AbstractMicroglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.

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