The Effect of Ribavirin on Reactive Astrogliosis in Experimental Autoimmune Encephalomyelitis

Lavrnja, Irena; Savić, Danijela; Bjelobaba, Ivana; Đačić, Sanja; Božić, Iva; Parabucki, Ana; Nedeljković, Nadežda; Peković, Sanja; Rakić, Ljubisav; Stojiljković, Mirjana

doi:10.1254/jphs.12004fp

Cited by 23 publications

(26 citation statements)

References 37 publications

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“…EAE was induced by intradermal injection of 100 μL emulsion of rat SCH (50% w/v in saline) and complete Freund's adjuvant containing 1 mg/ml Mycobacterium tuberculosis (Sigma, St. Louis, MO), divided into two halves, and injected in both hind footpads in groups 2–4 …”

Section: Methodsmentioning

confidence: 85%

The neuroprotective effect of mesenchymal stem cells on an experimentally induced model for multiple sclerosis in mice

Mahfouz

Abdelsalam

Masoud

et al. 2017

J Biochem Mol Toxicol

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Multiple sclerosis (MS) is a chronic autoimmune demyelinating neurodegenerative central nervous system disorder. The aim of the present study was to investigate the prophylactic effect exerted by the one-time intraperitoneal injection of mesenchymal stem cells (MSCs) 1 × 10 and 14-day intraperitoneal injection of methylprednisolone (MP) 40 mg/kg in an experimental autoimmune encephalomyelitis (EAE). EAE was induced by intradermal injection of rat spinal cord homogenate with complete Freund's adjuvant in Swiss mice. Results of MSCs and MP-treated mice showed a significantly milder disease and fewer clinical scores compared to control mice. They suppressed tumor necrosis factor-alpha and myeloperoxidase and increased interleukin 10, whereas thiobarbituric acid reactive substances and nitric oxide brain contents were reduced to comparable levels between treatment groups. Brain content of GSH was significantly higher in MSCs-treated mice than control mice. It is evident that MSCs have relevant prophylactic effect in an animal model of MS and might represent a valuable tool for stem cell based therapy in MS.

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Section: Methodsmentioning

confidence: 85%

The neuroprotective effect of mesenchymal stem cells on an experimentally induced model for multiple sclerosis in mice

Mahfouz

Abdelsalam

Masoud

et al. 2017

J Biochem Mol Toxicol

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“…At the onset of clinical deficits in EAE animals, astrocytes start to proliferate, while elongated fibrous branches border inflammatory infiltrates (Lavrnja et al, ). During the inflammatory phase of the disease, astrocytes undergo massive proliferation and extensive hypertrophy of cell bodies with enlarged intertwining processes, forming the scar border (Lavrnja et al, ). Scar formation is a physical border composed of reactive astrocytes that demark and divide an injured area from the normal‐appearing tissue, resulting in extracellular matrix composition changes, which prevent remyelination (Miljkovic, Timotijevic, & Mostarica Stojkovic, ).…”

Section: Experimental Autoimmune Encephalomyelitismentioning

confidence: 99%

“…In addition, MBP 87–99 failed to induce disease in DA rats but generated acute monophasic disease in Lewis rats (Stepaniak et al, ). Acute monophasic disease can be induced using whole spinal cord homogenate combined with CFA (Lavrnja et al, ), where the severity of disease is dependent on the amount of additionally administered M. tuberculosis (Milicevic et al, ). It was also reported that in DA rats, the homologous, rather than heterologous, tissue is a more efficient encephalitogen (Stosic‐Grujicic, Ramic, Bumbasirevic, Harhaji, & Mostarica‐Stojkovic, ).…”

Section: Selection Of Animals In Eaementioning

confidence: 99%

Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis

Bjelobaba

Begović-Kuprešanin

Peković

et al. 2018

J of Neuroscience Research

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137

102

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Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients. This review focuses on EAE because it represents both clinical and pathological features of MS. During the past decades, EAE has been effective in illuminating various pathological processes that occur during MS, including inflammation, CNS penetration, demyelination, axonopathy, and neuron loss mediated by immune cells.

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“…It was proposed that the availability of cholesterol is crucial for myelin membrane growth 52 and astrocytes have been described as an important source of cholesterol for neurons 53 . Previously, we have shown an increase of GFAP gene and protein expression at the end of EAE, suggesting astrocytes involvement in neuroprotection 50 and possibly in lipid trafficking 54 . The novel finding of this study is the association of CYP46A1 with reactive astrocytes surrounding demyelination plaques in the spinal cord of EAE rats, where those astrocytes are probably involved in clearance of axonal and myelin debris.…”

Section: Discussionmentioning

confidence: 80%

“…During MS or EAE, astrocytes undergo proliferation and extensive hypertrophy of cell bodies, accompanied by thickening and elongation of their processes 49 . Activated astrocytes in EAE and MS are associated with the glial scar formation, where a physical border composed of hypertrophic astrocytes separates an area of CNS damage from normal appearing tissue 50 , resulting in the extracellular matrix composition changes, which prevent remyelination 51 . It was proposed that the availability of cholesterol is crucial for myelin membrane growth 52 and astrocytes have been described as an important source of cholesterol for neurons 53 .…”

Section: Discussionmentioning

confidence: 99%

Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord

Lavrnja

Smiljanić

Savić

et al. 2017

Sci Rep

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Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease. The presence of myelin lipid debris was seen only at the peak of EAE in demyelination loci being efficiently removed during the recovery period. Since CYP46A1 is responsible for removal of cholesterol excess, we performed a detailed profiling of CYP46A1 expression and revealed regional and temporal specificities in its distribution. Double immunofluorescence staining demonstrated CYP46A1 localization with neurons, infiltrated macrophages, microglia and astrocytes in the areas of demyelination, suggesting that these cells play a role in cholesterol turnover in EAE. We propose that alterations in the regulation of cholesterol metabolism at the onset and peak of EAE may add to the progression of disease, while during the recovery period may have beneficial effects contributing to the regeneration of myelin sheath and restoration of neuronal function.

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The Effect of Ribavirin on Reactive Astrogliosis in Experimental Autoimmune Encephalomyelitis

Cited by 23 publications

References 37 publications

The neuroprotective effect of mesenchymal stem cells on an experimentally induced model for multiple sclerosis in mice

The neuroprotective effect of mesenchymal stem cells on an experimentally induced model for multiple sclerosis in mice

Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis

Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord

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