Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest 2008 Apr;118(4):1532-43
Date
03/15/2008Pubmed ID
18340379Pubmed Central ID
PMC2267014DOI
10.1172/JCI33464Scopus ID
2-s2.0-41849124231 (requires institutional sign-in at Scopus site) 215 CitationsAbstract
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.
Author List
Basso AS, Frenkel D, Quintana FJ, Costa-Pinto FA, Petrovic-Stojkovic S, Puckett L, Monsonego A, Bar-Shir A, Engel Y, Gozin M, Weiner HLAuthor
Lindsay L. Puckett MD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid Transport System X-AGAnimals
Astrocytes
Axons
B-Lymphocytes
CD11b Antigen
Chemokine CCL2
Chronic Disease
Disease Models, Animal
Disease Progression
Fullerenes
Glutamic Acid
Memory
Mice
Molecular Structure
Multiple Sclerosis
Oxidative Stress
T-Lymphocytes
