scholarly journals Effect of Carvacrol on Inflammatory Factors and Myelin Repair in Experimental Autoimmune Encephalomyelitis on Female Lewis Rats

2021 ◽  
Author(s):  
Mahdie Ahmadi ◽  
Akram Eidi ◽  
Mojtaba Khaksarian ◽  
Hassan Ahmadvand ◽  
Fattah Sotoodehnejadnematalahi
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Treated Group ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Myelin Repair ◽  
Experimental Autoimmune

Abstract Carvacrol is a phenolic monoterpene constituent of essential oils produced by plants such as Nigella sativa. This study examined the therapeutic effects of carvacrol in a model of experimental autoimmune encephalomyelitis (EAE). EAE induction was performed on female Lewis rats and, after appearance of the first clinical signs, a second EAE group received carvacrol intraperitoneally each day for 17 days. Clinical symptoms and body weight were assessed daily. All animals sacrificed and histological and gene expression analysis of the spinal cord were performed. The carvacrol treated group scored lower for disease after therapeutic administration than the control group. Gene expression analysis on the carvacrol treated group showed a decrease in TNF-α, NF-ҚB and IL-17 (pro-inflammatory) gene expression and an increase in MBP and OLIG2 remyelination markers. In the carvacrol treated group, H&E stain of spinal cord sections revealed a remarkable decrease in the amount of inflammatory cell infiltration. Immunostaining of lumbar spinal cord sections demonstrated a remarkable increase in MBP and a decrease in IL-17 secretion in the carvacrol treated group. These results demonstrate that carvacrol had a beneficial therapeutic effect and anti-inflammatory properties that significantly reduced the clinical scores and promoted myelin repair.

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.

Immunohistochemical study of flotillin-1 in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis

2006 ◽  
Vol 1114 (1) ◽  
pp. 204-211 ◽  
Author(s):  
Heechul Kim ◽  
Meejung Ahn ◽  
Changjong Moon ◽  
Yoh Matsumoto ◽  
Chang Sung Koh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immunohistochemical Study ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

scholarly journals Expression of Erythropoietin in the Spinal Cord of Lewis Rats with Experimental Autoimmune Encephalomyelitis

2009 ◽  
Vol 5 (1) ◽  
pp. 39 ◽  
Author(s):  
Sa-Yoon Kang ◽  
Ji-Hoon Kang ◽  
Jay Chol Choi ◽  
Jung Seok Lee ◽  
Chang Sub Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Experimental Autoimmune

Increased phosphorylation of caveolin-1 in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis

2006 ◽  
Vol 402 (1-2) ◽  
pp. 76-80 ◽  
Author(s):  
Heechul Kim ◽  
Meejung Ahn ◽  
Jeeyoung Lee ◽  
Changjong Moon ◽  
Yoh Matsumoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Lewis Rats ◽  
Caveolin 1 ◽  
Experimental Autoimmune

scholarly journals Efficacy of vafidemstat in experimental autoimmune encephalomyelitis highlights the KDM1A/RCOR1/HDAC epigenetic axis in multiple sclerosis

2021 ◽  
Author(s):  
Fernando Cavalcanti ◽  
Elena Gonzalez-Rey ◽  
Mario Delgado ◽  
Leyre Mestre ◽  
Carmen Guaza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gene Expression Signature ◽  
Autoimmune Encephalomyelitis ◽  
Theiler's Murine Encephalomyelitis Virus ◽  
Theiler’S Murine Encephalomyelitis Virus ◽  
Encephalomyelitis Virus ◽  
Experimental Autoimmune

Abstract Background Vafidemstat (ORY-2001) is a clinical stage inhibitor of the Lysine Specific Demethylase KDM1A in development for treatment of neurodegenerative and psychiatric diseases. KDM1A demethylates H3K4me1/2 and together with the histone deacetylases HDAC1/2, it forms part of co-repressor complexes recruited by zinc finger factors to control transcription. The exact role of KDM1A in neuroinflammation remained to be explored. Methods Compounds were administered p.o. gavage to mice with MOG35-55 induced experimental autoimmune encephalomyelitis or mice infected with Theiler’s murine encephalomyelitis virus. Immune cell infiltration was analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by ELISA. Genome wide gene expression in spinal cord and brain were analyzed by two-color microarray analysis and qRT-PCR. Results ORY-2001 improved the clinical score in mouse experimental autoimmune encephalomyelitis and in mice infected with the Theiler’s murine encephalomyelitis virus. The compound reduced lymphocyte egress and infiltration of immune cells in the spinal cord and prevented demyelination. ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the induction of the inflammatory gene expression signature in the central nervous system more potently. Gene expression changes and axonal protection in animals, and protection against glutamate excitoxicity in spinal cord explants support that ORY-2001 has neuroprotective qualities. Conclusions ORY-2001 exerts therapeutic activity in two mouse models of multiple sclerosis. The anti-inflammatory properties of ORY-2001 are being tested in a Phase IIa clinical trial in patients with relapse remitting and secondary progressive multiple sclerosis, and in severely ill COVID-19 patients at risk for acute respiratory distress syndrome.

scholarly journals Efficacy of vafidemstat in experimental autoimmune encephalomyelitis highlights the KDM1A/RCOR1/HDAC epigenetic axis in multiple sclerosis

2020 ◽  
Author(s):  
Fernando Cavalcanti ◽  
Elena Gonzalez-Rey ◽  
Mario Delgado ◽  
Leyre Mestre ◽  
Carmen Guaza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gene Expression Signature ◽  
Autoimmune Encephalomyelitis ◽  
Theiler's Murine Encephalomyelitis Virus ◽  
Theiler’S Murine Encephalomyelitis Virus ◽  
Encephalomyelitis Virus ◽  
Experimental Autoimmune

Abstract Background Vafidemstat (ORY-2001) is a clinical stage inhibitor of the Lysine Specific Demethylase KDM1A in development for treatment of neurodegenerative and psychiatric diseases. KDM1A demethylates H3K4me1/2 and together with the histone deacetylases HDAC1/2, it forms part of co-repressor complexes recruited by zinc finger factors to control transcription. The exact role of KDM1A in neuroinflammation remained to be explored. Methods Compounds were administered p.o. gavage to mice with MOG35-55 induced experimental autoimmune encephalomyelitis or mice infected with Theiler’s murine encephalomyelitis virus. Immune cell infiltration was analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by ELISA. Genome wide gene expression in spinal cord and brain were analyzed by two-color microarray analysis and qRT-PCR.Results ORY-2001 improved the clinical score in mouse experimental autoimmune encephalomyelitis and in mice infected with the Theiler’s murine encephalomyelitis virus. The compound reduced lymphocyte egress and infiltration of immune cells in the spinal cord and prevented demyelination. ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the induction of the inflammatory gene expression signature in the central nervous system more potently. Gene expression changes and axonal protection in animals, and protection against glutamate excitoxicity in spinal cord explants support that ORY-2001 has neuroprotective qualities.Conclusions ORY-2001 exerts therapeutic activity in two mouse models of multiple sclerosis. The anti-inflammatory properties of ORY-2001 are being tested in a Phase IIa clinical trial in patients with relapse remitting and secondary progressive multiple sclerosis, and in severely ill COVID-19 patients at risk for acute respiratory distress syndrome.

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