scholarly journals Monitoring diffuse injury during disease progression in experimental autoimmune encephalomyelitis with on resonance variable delay multiple pulse (onVDMP) CEST MRI

NeuroImage ◽  
2020 ◽  
Vol 204 ◽  
pp. 116245 ◽  
Author(s):  
Aline M. Thomas ◽  
Jiadi Xu ◽  
Peter A. Calabresi ◽  
Peter C.M. van Zijl ◽  
Jeff W.M. Bulte
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Wen-Tsan Weng ◽  
Ping-Chang Kuo ◽  
Dennis A. Brown ◽  
Barbara A. Scofield ◽  
Destin Furnas ◽  
...  

Abstract Background Multiple sclerosis (MS) is a progressive autoimmune disease characterized by the accumulation of pathogenic inflammatory immune cells in the central nervous system (CNS) that subsequently causes focal inflammation, demyelination, axonal injury, and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model that mimics the key features of MS. Presently, the dietary consumption of foods rich in phenols has been reported to offer numerous health benefits, including anti-inflammatory activity. One such compound, 4-ethylguaiacol (4-EG), found in various foods, is known to attenuate inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects on modulating the CNS inflammatory immune responses remains unknown. Thus, in this study, we assessed the therapeutic effect of 4-EG in EAE using both chronic and relapsing-remitting animal models and investigated the immunomodulatory effects of 4-EG on neuroinflammation and Th1/Th17 differentiation in EAE. Methods Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced followed by 4-EG treatment. The effects of 4-EG on disease progression, peripheral Th1/Th17 differentiation, CNS Th1/Th17 infiltration, microglia (MG) activation, and blood-brain barrier (BBB) disruption in EAE were evaluated. In addition, the expression of MMP9, MMP3, HO-1, and Nrf2 was assessed in the CNS of C57BL/6 EAE mice. Results Our results showed that 4-EG not only ameliorated disease severity in C57BL/6 chronic EAE but also mitigated disease progression in SJL/J relapsing-remitting EAE. Further investigations of the cellular and molecular mechanisms revealed that 4-EG suppressed MG activation, mitigated BBB disruption, repressed MMP3/MMP9 production, and inhibited Th1 and Th17 infiltration in the CNS of EAE. Furthermore, 4-EG suppressed Th1 and Th17 differentiation in the periphery of EAE and in vitro Th1 and Th17 cultures. Finally, we found 4-EG induced HO-1 expression in the CNS of EAE in vivo as well as in MG, BV2 cells, and macrophages in vitro. Conclusions Our work demonstrates that 4-EG confers protection against autoimmune disease EAE through modulating neuroinflammation and inhibiting Th1 and Th17 differentiation, suggesting 4-EG, a natural compound, could be potentially developed as a therapeutic agent for the treatment of MS/EAE.


2021 ◽  
Vol 361 ◽  
pp. 577730
Author(s):  
Julia P. Segal ◽  
Sarah Phillips ◽  
Rosalin M. Dubois ◽  
Jaqueline R. Silva ◽  
Cortney M. Haird ◽  
...  

2013 ◽  
Vol 38 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Darpan I. Patel ◽  
Lesley J. White

The impact of exercise on disease progression in multiple sclerosis (MS) is unclear. In the present study, we evaluated the clinical effects of forced wheel running on rats induced with experimental autoimmune encephalomyelitis (EAE), a model of MS. Female Lewis rats (n = 40) were randomly assigned to 1 of 4 groups prior to inoculation: EAE exercise (EAE-Ex), EAE sedentary (EAE-Sed), control exercise (Con-Ex), or control sedentary (Con-Sed). Exercise training was composed of forced treadmill running at increasing intensity across 10 consecutive days. No significant differences in clinical disability were observed in the EAE groups at the conclusion of this study. Furthermore, no significant differences in brain mass were observed across groups. Analysis of brain tissue proteins revealed that tumour necrosis factor-α (TNF-α) concentrations were higher in both EAE groups compared with the control groups (p < 0.05); however, no significant differences were seen between the EAE-Ex and EAE-Sed groups. The Con-Ex group had lower whole-brain TNF-α compared with the Con-Sed group (p < 0.05). Nerve growth factor concentrations were greater in the EAE-Ex animals compared with both control groups (p < 0.05 for both). No differences were seen in brain-derived neurotrophic factor. Our results indicate that aerobic exercise can modulate the proteins associated with disability in EAE; however, further research is required to understand the total impact of exercise on EAE disability and disease progression.


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