Reciprocal stimulation between TNF-α and nitric oxide may exacerbate CNS inflammation in experimental autoimmune encephalomyelitis

1998 ◽  
Vol 89 (1-2) ◽  
pp. 122-130 ◽  
Author(s):  
Deming Sun ◽  
Christopher Coleclough ◽  
Ligong Cao ◽  
Xianzhen Hu ◽  
Sheher Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Tnf Α ◽  
Experimental Autoimmune

scholarly journals Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Su Zhang ◽  
Quan-Cheng Kan ◽  
Yuming Xu ◽  
Guang-Xian Zhang ◽  
Lin Zhu
Keyword(s):  
Basement Membrane ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Blood Brain Barrier ◽  
Adaptor Protein ◽  
Brain Barrier ◽  
Autoimmune Encephalomyelitis ◽  
Novel Therapy ◽  
Cns Inflammation ◽  
Blood Brain ◽  
Experimental Autoimmune

Dysfunction of the blood-brain barrier (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX) in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement membrane, and the structure of tight junction (TJ) adaptor protein Zonula occludens-1 (ZO-1). Furthermore, MAT treatment attenuated expression of matrix metalloproteinase-9 and -2 (MMP-9/-2), while it increased the expression of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1/-2). Our findings demonstrate that MAT reduces BBB leakage by strengthening basement membrane, inhibiting activities of MMP-2 and -9, and upregulating their inhibitors. Taken together, our results identify a novel mechanism underlying the effect of MAT, a natural compound that could be a novel therapy for MS.

Modulation of experimental autoimmune encephalomyelitis through colonisation of the gut with Escherichia coli

2020 ◽  
pp. 1-16 ◽  
Author(s):  
J.E. Libbey ◽  
J.M.S. Sanchez ◽  
B.A. Fleming ◽  
D.J. Doty ◽  
A.B. DePaula-Silva ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Probiotic Bacterium ◽  
Coli Strain ◽  
Preclinical Model ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a neuro-inflammatory autoimmune disease of the central nervous system (CNS) that affects young adults. It is characterised by the development of demyelinating lesions and inflammation within the CNS. Although the causes of MS are still elusive, recent work using patient samples and experimental animal models has demonstrated a strong relationship between the gut microbiota and its contribution to CNS inflammation and MS. While there is no cure for MS, alteration of the gut microbiota composition through the use of probiotics is a very promising treatment. However, while most recent works have focused on the use of probiotics to modify pre-existing disease, little is known about its role in protecting from the establishment of MS. In this study, we determined whether colonisation with the probiotic bacterium Escherichia coli strain Nissle 1917 (EcN) could be used as a prophylactic strategy to prevent or alter the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We found that double gavage (two doses) of EcN before induction of EAE delayed disease onset and decreased disease severity. We also found that EcN-treated mice had decreased amounts of perivascular cuffing, CD4+ T cell infiltration into the CNS, together with significantly decreased absolute numbers of Th1 cells, and reduced activation of microglia. Although further studies are necessary to comprehend the exact protective mechanisms induced, our study supports a promising use of EcN as a probiotic for the prevention of MS.

scholarly journals Intravenous Liposomal Prednisolone Downregulates In Situ TNF-α Production by T-cells in Experimental Autoimmune Encephalomyelitis

2003 ◽  
Vol 51 (9) ◽  
pp. 1241-1244 ◽  
Author(s):  
Jens Schmidt ◽  
Josbert M. Metselaar ◽  
Ralf Gold
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
High Dose ◽  
Autoimmune Encephalomyelitis ◽  
Double Labeling ◽  
Formalin Fixed Paraffin ◽  
Tnf Α ◽  
Formalin Fixed Paraffin Embedded ◽  
Factor Α ◽  
Experimental Autoimmune

Multiple sclerosis (MS) relapses are treated with high-dose IV glucocorticosteroids. Here we investigated mechanisms of long-circulating polyethylene glycol-coated liposomes encapsulating prednisolone (PL) in adoptive transfer experimental autoimmune encephalomyelitis. Rats received IV 10 mg/kg PL 6, 18, or 42 hr before sacrifice at disease maximum. In formalin-fixed, paraffin-embedded spinal cord we employed a nonfluorescent immunohistochemical (IHC) double labeling. We stained for tumor necrosis factor-α (TNF-α) in combination with a T-cell antigen. Compared with PBS-containing liposomes, PL at 18 hr, and more at 42 hr, significantly reduced the rate of TNF-α double-labeled T-cells. This correlated with an ameliorated disease score at day 5 after PL 42 hr. Our results help to further understand mechanisms of action of drug targeting by liposomal steroids, with possible implications for treatment of autoimmune disorders such as MS.

Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis

2011 ◽  
Vol 25 (6) ◽  
pp. 1242-1248 ◽  
Author(s):  
Silvia Rossi ◽  
Roberto Furlan ◽  
Valentina De Chiara ◽  
Luca Muzio ◽  
Alessandra Musella ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Cb1 Receptors ◽  
Autoimmune Encephalomyelitis ◽  
Tnf Α ◽  
Experimental Autoimmune
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