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Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis.

Basso, Alexandre S. and Frenkel, Dan and Quintana, Francisco J. and Costa-Pinto, Frederico A. and Petrovic-Stojkovic, Sanja and Puckett, Lindsay and Monsonego, Alon and Bar-Shir, Amnon and Engel, Yoni and Gozin, Michael and Weiner, Howard L. (2008) Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. The Journal of clinical investigation, 118 (4). pp. 1532-43. ISSN 0021-9738

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Official URL: http://www.jci.org/articles/view/33464

Abstract

Axonal degeneration is an important determinant of progressive neurological disability in multiple sclerosis (MS). Thus, therapeutic approaches promoting neuroprotection could aid the treatment of progressive MS. Here, we used what we believe is a novel water-soluble fullerene derivative (ABS-75) attached to an NMDA receptor antagonist, which combines antioxidant and anti-excitotoxic properties, to block axonal damage and reduce disease progression in a chronic progressive EAE model. Fullerene ABS-75 treatment initiated after disease onset reduced the clinical progression of chronic EAE in NOD mice immunized with myelin-oligodendrocyte glycoprotein (MOG). Reduced disease progression in ABS-75-treated mice was associated with reduced axonal loss and demyelination in the spinal cord. Fullerene ABS-75 halted oxidative injury, CD11b+ infiltration, and CCL2 expression in the spinal cord of mice without interfering with antigen-specific T cell responses. In vitro, fullerene ABS-75 protected neurons from oxidative and glutamate-induced injury and restored glutamine synthetase and glutamate transporter expression in astrocytes under inflammatory insult. Glutamine synthetase expression was also increased in the white matter of fullerene ABS-75-treated animals. Our data demonstrate the neuroprotective effect of treatment with a fullerene compound combined with a NMDA receptor antagonist, which may be useful in the treatment of progressive MS and other neurodegenerative diseases.

Item Type:Article
Subjects:Biomedical Science > Nanobiotechnology
Biomedical Science > Nanotechnology for human health
ID Code:82
Deposited By:Lesley Tobin
Deposited On:08 Jan 2009 12:01
Last Modified:12 Feb 2009 15:41

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