stilbenes and Multiple-Sclerosis

Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base.. We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxidants in MS.. Using predefined criteria, we searched key databases. Two authors scrutinized all studies against inclusion/exclusion criteria, assessed study risk-of-bias and extracted results.. Of the 3507 titles, 145 met criteria and included compounds, α(alpha)-lipoic acid (ALA), anti-oxidant vitamins, Ginkgo biloba, quercetin, resveratrol and epigallocatechin-3-gallate (ECGC). The strongest evidence to support OTC anti-oxidants was for compounds EGCG and ALA in animal models; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment. Only vitamin E, Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit.. OTC anti-oxidants EGCG and ALA show the most consistent benefit, however only in preclinical studies. There is no evidence that they alter MS relapses or progression. Future work should focus on testing more of these therapies for clinical efficacy before recommending them to MS patients.

Topics: Animals; Antioxidants; Catechin; Ginkgo biloba; Humans; Multiple Sclerosis; Nonprescription Drugs; Quercetin; Resveratrol; Stilbenes; Thioctic Acid

Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter.. We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer. We report the findings of amyloid PET in a patient with pseudotumoral multiple sclerosis. This case provides further evidence on the role of amyloid PET in the assessment of white matter and demyelinating diseases.

Topics: Aniline Compounds; Brain; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Multiple Sclerosis; Positron-Emission Tomography; Stilbenes; White Matter

Multiple sclerosis (MS) is a demyelinating neurodegenerative disease, representing a major cause of neurological disability in young adults. Resveratrol is a stilbenoid polyphenol, known to pass blood brain barrier and exhibit antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. Cuprizone model of MS is particularly beneficial in studying demyelination/remyelination. Our study examined the potential neuroprotective and pro-remyelination effects of resveratrol in cuprizone-intoxicated C57Bl/6 mice. Mice were fed with chow containing 0.7 % cuprizone for 7 days, followed by 3 weeks on 0.2 % cuprizone diet. Resveratrol (250 mg/kg/day, p.o.) was given for 3 weeks starting from the second week. At the end of the experiment, animals were tested on rotarod to evaluate changes in balance and motor coordination. Mice were then sacrificed to measure the brain content of glutathione, lipid peroxidation products, adenosine triphosphate, and phospho-inhibitory subunit of nuclear factor κB-α. The activities of cytochrome oxidase and superoxide dismutase were also assessed. The gene expression of myelin basic protein, 2',3'-cyclic nucleotide 3' phosphodiesterase, oligodendrocyte transcription factor-1 (Olig1), NF-κB p65 subunit, and tumor necrosis factor-α was also estimated. Luxol fast blue/periodic acid-Schiff stained brain sections were blindly scored to assess the myelin status. Resveratrol effectively enhanced motor coordination and balance, reversed cuprizone-induced demyelination, improved mitochondrial function, alleviated oxidative stress, and inhibited NF-κB signaling. Interestingly, resveratrol increased Olig1 expression that is positively correlated to active remyelination. The present study may be the first to indicate a pro-remyelinative effect for resveratrol which might represent a potential additive benefit in treating MS.

Topics: Animals; Biomarkers; Brain; Cuprizone; Disease Models, Animal; Inflammation; Male; Mice, Inbred C57BL; Mitochondria; Motor Activity; Multiple Sclerosis; Myelin Sheath; Oxidative Stress; Remyelination; Resveratrol; Stilbenes

Topics: Benzothiazoles; Humans; Multiple Sclerosis; Myelin Sheath; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

Positron emission tomography (PET) images with amyloid tracers show normal uptake in healthy white matter, which suggests that amyloid tracers are potentially useful for studying such white matter diseases as multiple sclerosis (MS).. Twelve patients diagnosed with MS (5 with RRMS, 5 with SPMS, and 2 with PPMS) and 3 healthy controls underwent studies with MRI and (18)F-florbetaben-PET imaging. Images were preprocessed using Statistical Parametric Mapping software. We analysed (18)F-florbetaben uptake in demyelinating plaques (appearing as hyperintense lesions in FLAIR sequences), in normal-appearing white matter, and in grey matter.. Mean standardized uptake value relative to cerebellum was higher in normally appearing white matter (NAWM) (1.51 ± 0.12) than in damaged white matter (DWM) (1.24 ± 0.12; P = .002). Mean percentage of change between NAWM and DWM was -17.56% ± 6.22%. This percentage of change correlated negatively with EDSS scores (r = -0.61, p < .05) and with age (r = -0.83, p < 0.01). Progressive forms of MS showed a more pronounced reduction of the uptake in DWM in comparison to relapsing-remitting form.. Uptake of (18)F-florbetaben in damaged white matter is lower than that occurring in normally-appearing white matter. These findings indicate that amyloid tracers may be useful in studies of MS, although further research is needed to evaluate the utility of amyloid-PET in monitoring MS progression.

Topics: Adult; Amyloid; Aniline Compounds; Female; Fluorine Radioisotopes; Gray Matter; Humans; Male; Middle Aged; Multiple Sclerosis; Positron-Emission Tomography; Stilbenes; White Matter

In this study, we compared the ability of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake.. Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group).. The kinetics of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [(11)C]CIC make this tracer less suitable for in vivo PET imaging. [(11)C]PIB showed good uptake in the white matter in the cerebrum, but [(11)C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [(11)C]MeDAS distribution correlated well with myelin density in different brain regions.. This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [(11)C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [(11)C]CIC and [(11)C]PIB.

Topics: Aniline Compounds; Animals; Benzothiazoles; Encephalomyelitis, Autoimmune, Experimental; Male; Multiple Sclerosis; Myelin Sheath; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Stilbenes; Thiazoles

The polyphenol compound resveratrol is reported to have multiple functions, including neuroprotection, and no major adverse effects have been reported. Although the neuroprotective effects have been associated with sirtuin 1 activation by resveratrol, the mechanisms by which resveratrol exerts such functions are a matter of controversy. We examined whether resveratrol can be neuroprotective in two models of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). EAE was induced in C57BL/6 mice, which were fed a control diet or a diet containing resveratrol during either the induction or effector phase or through the whole course of EAE. SJL/J mice were infected with TMEV and fed a control diet or a diet containing resveratrol during the chronic phase of TMEV-IDD. In EAE, all groups of mice treated with resveratrol had more severe clinical signs than the control group. In particular, resveratrol treatment during the induction phase resulted in the most severe EAE, both clinically and histologically. Similarly, in the viral model, the mice treated with resveratrol developed significantly more severe TMEV-IDD than the control group. Thus, surprisingly, the resveratrol treatment significantly exacerbated demyelination and inflammation without neuroprotection in the central nervous system in both models. Our findings indicate that caution should be exercised in potential therapeutic applications of resveratrol in human inflammatory demyelinating diseases, including multiple sclerosis.

Topics: Animals; Autoimmunity; Axons; Disease Models, Animal; Disease Progression; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Nerve Degeneration; Neuroprotective Agents; Resveratrol; Stilbenes; Theilovirus; Virulence

Topics: Animals; Cell Survival; Encephalomyelitis, Autoimmune, Experimental; Female; Humans; Multiple Sclerosis; Nerve Degeneration; Nerve Regeneration; Optic Nerve; Optic Nerve Diseases; Resveratrol; Retinal Ganglion Cells; Stilbenes

Neuronal loss in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), correlates with permanent neurological dysfunction. Current MS therapies have limited the ability to prevent neuronal damage.. We examined whether oral therapy with SRT501, a pharmaceutical grade formulation of resveratrol, reduces neuronal loss during relapsing-remitting EAE. Resveratrol activates SIRT1, an NAD+-dependent deacetylase that promotes mitochondrial function.. Oral SRT501 prevented neuronal loss during optic neuritis, an inflammatory optic nerve lesion in MS and EAE. SRT501 also suppressed neurological dysfunction during EAE remission, and spinal cords from SRT501-treated mice had significantly higher axonal density than vehicle-treated mice. Similar neuroprotection was mediated by SRT1720, another SIRT1-activating compound; and sirtinol, an SIRT1 inhibitor, attenuated SRT501 neuroprotective effects. SIRT1 activators did not prevent inflammation.. These studies demonstrate that SRT501 attenuates neuronal damage and neurological dysfunction in EAE by a mechanism involving SIRT1 activation. SIRT1 activators are a potential oral therapy in MS.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Mice; Multiple Sclerosis; Nerve Degeneration; Resveratrol; Stilbenes

Promoting myelin repair is one of the most promising therapeutic avenues in the field of myelin disorders. In future clinical trials, evaluation of remyelination will require a reliable and quantifiable myelin marker to be used as a surrogate marker. To date, MRI assessment lacks specificity for evaluating the level of remyelination within the brain. Here, we describe 1,4-bis(p-aminostyryl)-2-methoxy benzene (BMB), a synthesized fluorescent molecule, that binds selectively to myelin both ex vivo and in vivo. The binding of BMB to myelin allows the detection of demyelinating lesions in an experimental autoimmune encephalitis model of demyelination and allows a mean for quantifying myelin loss in dysmyelinating mutants. In multiple sclerosis brain, different levels of BMB binding differentiated remyelination in shadow plaques from either demyelinated lesions or normal-appearing white matter. After systemic injection, BMB crosses the blood-brain barrier and binds to myelin in a dose-dependent and reversible manner. Finally, we provide evidence that (11)C-radiolabeled BMB can be used in vivo to image CNS myelin by positron-emission tomography in baboon. Our results provide a perspective for developing a brain myelin imaging technique by positron-emission tomography.

Topics: Animals; Anisoles; Biomarkers; Carbon Radioisotopes; Central Nervous System; Encephalomyelitis, Autoimmune, Experimental; Fluorescent Dyes; Humans; Mice; Mice, Inbred C57BL; Molecular Structure; Multiple Sclerosis; Myelin Sheath; Papio anubis; Positron-Emission Tomography; Rats; Rats, Wistar; Stilbenes