Sato F.,Louisiana State University |
Martinez N.E.,Louisiana State University |
Shahid M.,Dow Medical College |
Rose J.W.,Neurovirology Research Laboratory |
And 5 more authors.
American Journal of Pathology | Year: 2013
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. Copyright © 2013 American Society for Investigative Pathology.
Ford C.,University of New Mexico |
Goodman A.D.,University of Rochester |
Johnson K.,University of Maryland, Baltimore |
Kachuck N.,University of Southern California |
And 11 more authors.
Multiple Sclerosis | Year: 2010
The ongoing US Glatiramer Acetate (GA) Trial is the longest evaluation of continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to evaluate up to 15 years of GA as a sole disease-modifying therapy. Two hundred and thirty-two patients received at least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%, Ongoing cohort) continued as of February 2008. Patients were evaluated every 6 months using the Expanded Disability Status Scale (EDSS). Mean GA exposures were 8.6 ± 5.2, 4.81 ± 3.69, and 13.6 ± 1.3 years and mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing cohorts, respectively. For Ongoing patients, annual relapse rates (ARRs) maintained a decline from 1.12 ± 0.82 at baseline to 0.25 ± 0.34 per year; 57% had stable/improved EDSS scores (change ≤ 0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8. For all patients on GA therapy (the mITT cohort), ARRs declined from 1.18 ± 0.82 to 0.43 ± 0.58 per year; 54% had stable/improved EDSS scores; 75% had not transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8. In conclusion, multiple sclerosis patients with mean disease duration of 22 years administering GA for up to 15 years had reduced relapse rates, and decreased disability progression and transition to SPMS. There were no long-term safety issues. © 2010 The Author(s).
Langer H.F.,U.S. National Institutes of Health |
Langer H.F.,University of Tübingen |
Choi E.Y.,U.S. National Institutes of Health |
Choi E.Y.,TU Dresden |
And 28 more authors.
Circulation Research | Year: 2012
Rationale: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. Objective: We addressed the role of platelets in mediating CNS inflammation in EAE. Methods and Results: We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control nondiseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression on platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ibα (GPIbα) promotes both platelet adhesion and inflammatory actions of platelets and targeting of GPIbα attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice. Conclusions: Platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment. © 2012 American Heart Association, Inc.
Yonnet G.J.,University of Utah |
Fjeldstad A.S.,University of Utah |
Carlson N.G.,Neurovirology Research Laboratory |
Rose J.W.,University of Utah |
Rose J.W.,Neurovirology Research Laboratory
International Journal of MS Care | Year: 2013
Bladder dysfunction in multiple sclerosis (MS) can be socially disabling, have negative psychological and economic consequences, and impair patients' quality of life. Knowledge of the functional anatomy and physiology of the urinary tract is essential to understand the symptoms associated with central nervous system lesions and the pharmacotherapies used to treat them. Treatments for neurogenic detrusor overactivity (NDO) have consisted mainly of administration of anticholinergic drugs, which have been shown to provide suboptimal clinical benefits and be poorly tolerated. The US Food and Drug Administration (FDA) approval of intravesicular botulinum toxin therapy provides a secondline option for MS patients with NDO not responsive to anticholinergic drugs. We performed a review of key literature pertaining to the intravesicular application of botulinum toxin. In the management of NDO, administration of intravesicular botulinum toxin using clean intermittent catheterization decreases the incidence of urinary tract infections, promotes urinary continence, and improves quality of life for 9 months after a single injection; moreover, those benefits are maintained with repeated injections over time. © 2013 Consortium of Multiple Sclerosis Centers.