Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis

Marracci, Gail; Jones, Richard E.; McKeon, Gabriel P; Bourdette, Dennis

doi:10.1016/s0165-5728(02)00269-2

Cited by 128 publications

(104 citation statements)

References 36 publications

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“…Our results demonstrated that water restriction and administration of saccharin flavored water did not cause development of overly mild or overly severe disease, and the previously demonstrated temporal link between clinical response and administration of ALA (Marracci et al, 2002) was retained in waterrestricted, saccharin-treated mice. Thus, effects of restricted water access and administration of saccharin-flavored water were minimal in this EAE model and would not be expected to interfere with detection of a conditioned therapeutic response during the testing period.…”

Section: Discussionsupporting

confidence: 70%

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Treatment of experimental autoimmune encephalomyelitis with alpha lipoic acid and associative conditioning

Jones

Moes

Zwickey

et al. 2008

Brain, Behavior, and Immunity

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We have initiated studies to evaluate the suitability of performing therapeutic conditioning trials in experimental autoimmune encephalomyelitis (EAE) mice treated with alpha lipoic acid (ALA). EAE was induced in SJL mice by active immunization with myelin antigen. Once daily subcutaneous injection of ALA served as the unconditional stimulus (US) administered with the conditional stimulus (CS) saccharin-flavored drinking water under a regimen of restricted water access. In the first study, we found that water restriction and saccharin administration were compatible with disease development and effective ALA treatment of EAE mice. In the second study, mice were conditioned to once daily administration of ALA paired with administration of saccharin flavored water (US + CS) on days 7 -16. Test trials spanned experimental days 17 -32 in groups receiving either saccharinflavored water (CS, in the experimental group) versus unflavored water (CSo, in the control group) and compared several measures of EAE severity using multivariate ANOVA (MANOVA). Reduced disease severity in the experimental group (US+CS:CS) compared to the control group (US+CS:CSo) suggested that conditioning had occurred. These results demonstrate an approach for conducting therapeutic conditioning trials in EAE mice and suggest considerations for future investigations.

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Section: Discussionsupporting

confidence: 70%

“…Alpha lipoic acid (ALA) is highly effective at suppressing or treating murine EAE in a dose dependent fashion (Marracci et al, 2002;Morini et al, 2004). We propose that ALA might serve as a suitable US with which to apply a behavioral conditioning approach for examining a conditioned pharmacotherapeutic response.…”

Section: Introductionmentioning

confidence: 99%

Treatment of experimental autoimmune encephalomyelitis with alpha lipoic acid and associative conditioning

Jones

Moes

Zwickey

et al. 2008

Brain, Behavior, and Immunity

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“…a-Lipoic acid and its reduced form DHLA were shown to inhibit T-cell migration into the spinal cord and suppressed clinical signs in murine EAE (Marracci et al, 2002). This finding indicates that these dietary compounds can interfere with inflammatory mechanisms.…”

Section: Dietary Compounds Targeting Different Pathomechanisms In Msmentioning

confidence: 87%

“…Furthermore, a-lipoic acid was effective in treating EAE by inhibiting T-cell trafficking into the spinal cord by inhibiting matrix metalloproteinase activation (Marracci et al, 2002). Furthermore, it has been precised that a-lipoic acid, like NAC , reduces MMP-9 activity, whereas DHLA does not (Marracci et al, 2004).…”

Section: Thiol-based Antioxidantsmentioning

confidence: 99%

Antioxidants and polyunsaturated fatty acids in multiple sclerosis

Meeteren¹,

Teunissen

Dijkstra

et al. 2005

Eur J Clin Nutr

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“…168 Many antioxidants have been suggested for use in PD, but have not reached human trials. For a more extensive review on antioxidant therapy in PD, the reader is referred to the recent review by Singh et al 169 The EAE models have been attenuated by multiple antioxidants including tirilizad mesylate, 148 n-acetylcysteine, 170 catalase, 171 butylated hydroxyanisole, 172 Euk-8, 173 alpha lipoate, 174 and a green tea analogue. 175 Care in applying antioxidant therapy to neurodegenerative disorders should be exercised; a recent meta-analysis identified an increased, all-cause mortality in patients in primary and secondary prevention trials treated with vitamins A and E, and beta carotine.…”

Section: Iron-related Neurotherapeuticsmentioning

confidence: 99%

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

et al. 2007

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Summary:Iron is important for brain oxygen transport, electron transfer, neurotransmitter synthesis, and myelin production. Though iron deposition has been observed in the brain with normal aging, increased iron has also been shown in many chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In vitro studies have demonstrated that excessive iron can lead to free radical production, which can promote neurotoxicity. However, the link between observed iron deposition and pathological processes underlying various diseases of the brain is not well understood. It is not known whether excessive in vivo iron directly contributes to tissue damage or is solely an epiphenomenon. In this article, we focus on the imaging of brain iron and the underlying physiology and metabolism relating to iron deposition. We conclude with a discussion of the potential implications of iron-related toxicity to neurotherapeutic development.

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Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis

Cited by 128 publications

References 36 publications

Treatment of experimental autoimmune encephalomyelitis with alpha lipoic acid and associative conditioning

Treatment of experimental autoimmune encephalomyelitis with alpha lipoic acid and associative conditioning

Antioxidants and polyunsaturated fatty acids in multiple sclerosis

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

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