Toxocara canis, a gastrointestinal parasite of canids, is also highly prevalent in many paratenic hosts, such as mice and humans. As with many other helminths, the infection is associated with immunomodulatory effects, which could affect other inflammatory conditions including autoimmune and allergic diseases. Here, we investigated the effect of T. canis infection on the course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Mice infected with 2 doses of 100 T. canis L3 larvae 5 weeks prior to EAE induction (the Tc+EAE group) showed higher EAE clinical scores and greater weight loss compared to the non-infected group with induced EAE (the EAE group). Elevated concentrations of all measured serum cytokines (IL-1α, IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) were observed in the Tc+EAE group compared to the EAE group. In the CNS, the similar number of regulatory T cells (Tregs; CD4+FoxP3+Helios+) but their decreased proportion from total CD4+ cells was found in the Tc+EAE group compared to the EAE group. This could indicate that the group Tc+EAE harboured significantly more CD4+ T cells of non-Treg phenotype within the affected CNS. Altogether, our results demonstrate that infection of mice with T. canis worsens the course of subsequently induced EAE. Further studies are, therefore, urgently needed to reveal the underlying pathological mechanisms and to investigate possible risks for the human population, in which exposure to T. canis is frequent.
- MeSH
- CD4-pozitivní T-lymfocyty patologie MeSH
- cytokiny MeSH
- encefalomyelitida autoimunitní experimentální * patologie MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- roztroušená skleróza * patologie MeSH
- Toxocara canis * MeSH
- toxokaróza * komplikace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of this study was to evaluate therapeutic potential of edaravone in the murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) and to expand the knowledge of its mechanism of action. Edaravone (6 mg/kg/day) was administered intraperitoneally from the onset of clinical symptoms until the end of the experiment (28 days). Disease progression was assessed daily using severity scores. At the peak of the disease, histological analyses, markers of oxidative stress (OS) and parameters of mitochondrial function in the brains and spinal cords (SC) of mice were determined. Gene expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha was determined at the end of the experiment. Edaravone treatment ameliorated EAE severity and attenuated inflammation in the SC of the EAE mice, as verified by histological analysis. Moreover, edaravone treatment decreased OS, increased the gene expression of the Nrf2 and HO-1, increased the activity of the mitochondrial complex II/III, reduced the activity of the mitochondrial complex IV and preserved ATP production in the SC of the EAE mice. In conclusion, findings in this study provide additional evidence of edaravone potential for the treatment of multiple sclerosis and expand our knowledge of the mechanism of action of edaravone in the EAE model.
- MeSH
- edaravon farmakologie MeSH
- encefalomyelitida autoimunitní experimentální * patologie MeSH
- encefalomyelitida * MeSH
- exprese genu MeSH
- faktor 2 související s NF-E2 genetika metabolismus MeSH
- hemoxygenasa-1 genetika metabolismus MeSH
- myši MeSH
- stupeň závažnosti nemoci MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Experimental autoimmune encephalomyelitis (EAE) represents the mouse model of multiple sclerosis, a devastating neurological disorder. EAE development and progression involves the infiltration of different immune cells into the brain and spinal cord. However, less is known about a potential role of eosinophil granulocytes for EAE disease pathogenesis. In the present study, we found enhanced eosinophil abundance accompanied by increased concentration of the eosinophil chemoattractant eotaxin-1 in the spinal cord in the course of EAE induced in C57BL/6 mice by immunization with MOG35-55 peptide. However, the absence of eosinophils did not affect neuroinflammation, demyelination and clinical development or severity of EAE, as assessed in ∆dblGATA1 eosinophil-deficient mice. Taken together, despite their enhanced abundance in the inflamed spinal cord during disease progression, eosinophils were dispensable for EAE development.
- MeSH
- chemokin CCL11 metabolismus MeSH
- encefalomyelitida autoimunitní experimentální krev diagnóza imunologie patologie MeSH
- eozinofily imunologie metabolismus MeSH
- glykoprotein v myelinu oligodendrocytů aplikace a dávkování imunologie MeSH
- lidé MeSH
- mícha imunologie patologie MeSH
- myši transgenní MeSH
- myši MeSH
- peptidové fragmenty aplikace a dávkování imunologie MeSH
- roztroušená skleróza krev diagnóza imunologie patologie MeSH
- stupeň závažnosti nemoci MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We aimed to determine whether 10 days of treadmill exercise can increase skeletal muscle mass and intramuscular concentrations of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE). Forty female Lewis rats were randomly assigned to either EAE sedentary (EAE-Sed), EAE exercise (EAE-Ex), Control sedentary (Con-Sed) and Control exercise (Con-Ex). Exercising animals completed a 10 day forced exercising training program. Hind limb skeletal muscles were excised and weighed with soleus muscle used for BDNF and NGF quantification. Statistical analysis was done using a one-way analysis of variance. Disability was more pronounced in the EAE-Ex group than in the EAE-Sed group. Exercising animals (EAE-Ex and Con-Ex) had significantly greater bilateral EDL, plantaris and gastrocnemius muscle mass compared to their sedentary animals (p=0.01). The EAE-Ex group had significantly higher NGF concentrations (1.98+/-0.3 pg/mg) compared to Con-Ex (0.96+/-0.07 pg/mg, p=0.003) and Con-Sed (1.2+/-0.2 pg/mg, p=0.04) groups. The main effect of exercise represented a significantly lower BDNF concentrations in the soleus of exercising animals compared to sedentary animals (p=0.03). Our study provides preliminary evidence that exercise increases skeletal muscle mass despite the early onset of disability in EAE animals.
- MeSH
- encefalomyelitida autoimunitní experimentální patologie terapie MeSH
- kondiční příprava zvířat metody MeSH
- kosterní svaly růst a vývoj patologie MeSH
- krysa rodu rattus MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- posuzování pracovní neschopnosti MeSH
- potkani inbrední LEW MeSH
- sedavý životní styl MeSH
- tělesná hmotnost MeSH
- terapie cvičením metody MeSH
- zadní končetina patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The impact of high-intensity exercise on disease progression and muscle contractile properties in experimental autoimmune encephalomyelitis (EAE) remains unclear. Control (CON) and EAE rats were divided into sedentary and exercise groups. Before onset (experiment 1, n=40) and after hindquarter paralysis (experiment 2, n=40), isokinetic foot extensor strength, cross sectional area (CSA) of tibialis anterior (TA), extensor digitorum longus (EDL) and soleus (SOL) and brain-derived neurotrophic factor (BDNF) levels were assessed. EAE reduced muscle fiber CSA of TA, EDL and SOL. In general, exercise was not able to affect CSA, whereas it delayed hindquarter paralysis peak. CON muscle work peaked and declined, while it remained stable in EAE. BDNF-responses were not affected by EAE or exercise. In conclusion, EAE affected CSA-properties of TA, EDL and SOL, which could, partly, explain the absence of peak work during isokinetic muscle performance in EAE-animals. However, exercise was not able to prevent muscle fiber atrophy.
- MeSH
- encefalomyelitida autoimunitní experimentální krev patologie patofyziologie MeSH
- kondiční příprava zvířat fyziologie MeSH
- kosterní svalová vlákna patologie fyziologie MeSH
- mozkový neurotrofický faktor krev MeSH
- náhodné rozdělení MeSH
- potkani inbrední LEW MeSH
- přijímání potravy MeSH
- progrese nemoci MeSH
- svalová síla MeSH
- tělesná hmotnost MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- demyelinizační nemoci metabolismus patologie ultrastruktura MeSH
- encefalomyelitida autoimunitní experimentální metabolismus patologie ultrastruktura MeSH
- lidé MeSH
- lipidy analýza MeSH
- mícha patologie MeSH
- morčata MeSH
- mozek patologie MeSH
- roztroušená skleróza metabolismus patologie ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- morčata MeSH
- zvířata MeSH
- MeSH
- demyelinizační nemoci enzymologie MeSH
- encefalomyelitida autoimunitní experimentální enzymologie patofyziologie patologie MeSH
- enzymy MeSH
- morčata MeSH
- mozek - chemie MeSH
- subcelulární frakce patofyziologie patologie MeSH
- svaly patofyziologie patologie MeSH
- synapse enzymologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- zvířata MeSH
A single subcutaneous inoculation with 0.02 mg of heterologous myelin basic protein (MBP) in combination with Freund's complete adjuvant resulted in clinical and histological manifestations of experimental allergic encephalomyelitis (EAE) in 80-90% of treated guinea pigs. Daily parenteral administration of levamisole and etimisole during the latent period produced a suppressive effect on EAE development, reducing morbidity and mortality rates and preventing pathomorphological changes in the CNS. Animals receiving the drugs had decreased delayed hypersensitivity reactions to MBP in vitro. Etimisole brought about a moderate decline in the formation of circulating anti-MBP antibodies, while levamisole did not affect the strength of the humoral response, something which confirmed the primary role of cell-mediated immune reactions in the CNS demyelinization process. The reported findings may be significant in developing therapeutic strategies with respect to demyelinization diseases.
- MeSH
- encefalomyelitida autoimunitní experimentální imunologie patologie MeSH
- etimizol farmakologie MeSH
- imidazoly farmakologie MeSH
- levamisol farmakologie MeSH
- makrofágy účinky léků imunologie MeSH
- mícha účinky léků patologie MeSH
- morčata MeSH
- tvorba protilátek MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- cholesterol analýza MeSH
- demyelinizační nemoci patologie MeSH
- encefalomyelitida autoimunitní experimentální metabolismus patologie MeSH
- fosfolipidy analýza MeSH
- glykolipidy analýza MeSH
- Haplorrhini MeSH
- lidé MeSH
- roztroušená skleróza metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- MeSH
- adrenokortikotropní hormon aplikace a dávkování farmakologie MeSH
- demyelinizační autoimunitní nemoci CNS etiologie patologie MeSH
- encefalomyelitida autoimunitní experimentální * enzymologie farmakoterapie patologie MeSH
- fosfolipasy A * diagnostické užití metabolismus MeSH
- imunohistochemie metody MeSH
- isoniazid aplikace a dávkování farmakologie MeSH
- morčata MeSH
- vakcíny proti antraxu aplikace a dávkování farmakologie MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH