This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Vladimirova, O. Articles by Kalman, B. Search for Related Content PubMed PubMed Citation Articles by Vladimirova, O. Articles by Kalman, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Multiple Sclerosis Social Bookmarking                   What's this?

Oxidative damage to DNA in plaques of MS brains

Center for Neurovirology, Allegheny University of the Health Sciences, Philadelphia

John O'Connor

Department of Health Policy and Clinical Outcomes, Thomas Jefferson University, Philadelphia, Pennsylvania

Alan Cahill

Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania

Hansjuerg Alder

Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania

Catalin Butunoi

Rocky Mountain Multiple Sclerosis Center, Englewood, Colorado, USA

Bernadette Kalman

Center for Neurovirology, Allegheny University of the Health Sciences, Philadelphia

A major cause of clinical disability in multiple sclerosis (MS) is related to a degenerative process in the central nervous system (CNS) which ultimately develops from a potentially reversible inflammation and demyelination. The mechanism of this degenerative process within MS lesions is not completely understood. We hypothesize that oxidative damage to DNA secondary to inflammation may contribute to irreversible tissue alterations in a plaque. To test this assumption, we determined the level of a DNA oxidative marker, 8-hydroxy-deoxy-guanosine (8-OH-dG) in the normal appearing white matter (NAWM), plaque and cortical regions of cerebella from MS patients who suffered from severe cerebellar symptoms during the course of the disease, and in NAWM and cortical regions of cerebella from non-neurological controls. We found a significant increase in DNA oxidation within plaques compared to NAWM specimens in MS cerebella. A tendency for increase of oxidative markers in normal appearing cortical tissues located in the proximity of MS plaques was also observed when compared to those in control cortical specimens. Oxidative damage to DNA in MS lesions, and in neuron rich areas located in the proximity of these lesions is likely related to the release of reactive oxygen species (ROS) and nitric oxide (NO) during inflammation in the brain. This biochemical impairment of DNA and of other macromolecules may contribute to the development of severe clinical disability through the induction of degenerative changes within and outside of plaques in MS brains.

Key Words: clinical disability • plaque • oxidative damage

Multiple Sclerosis, Vol. 4, No. 5, 413-418 (1998)
DOI: 10.1177/135245859800400503


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Sidoti, C. Antognelli, C. Rinaldi, R. D'Angelo, V. Dattola, P. Girlanda, V. Talesa, and A. Amato Glyoxalase I A111E, paraoxonase 1 Q192R and L55M polymorphisms: susceptibility factors of multiple sclerosis? Multiple Sclerosis, May 1, 2007; 13(4): 446 - 453. [Abstract] [PDF]

				J.A. Cabrera-Gomez, J. Galarraga-Inza, R.M. Coro-Antich, Y. Real-Gonzalez, M. Cristofol-Corominas, H. Gomez, K. Romero-Garcia, M.X. Gil-Gil, and A. Gonzalez-Quevedo Down's syndrome and neuromyelitis optica (Devic's disease). An autopsy-proven case Multiple Sclerosis, April 1, 2007; 13(3): 433 - 436. [Abstract] [PDF]

				G. Schreibelt, R. J. P. Musters, A. Reijerkerk, L. R. de Groot, S. M. A. van der Pol, E. M. L. Hendrikx, E. D. Dopp, C. D. Dijkstra, B. Drukarch, and H. E. de Vries Lipoic Acid Affects Cellular Migration into the Central Nervous System and Stabilizes Blood-Brain Barrier Integrity J. Immunol., August 15, 2006; 177(4): 2630 - 2637. [Abstract] [Full Text] [PDF]

				J. Imitola, T. Chitnis, and S. J. Khoury Insights Into the Molecular Pathogenesis of Progression in Multiple Sclerosis: Potential Implications for Future Therapies Arch Neurol, January 1, 2006; 63(1): 25 - 33. [Abstract] [Full Text] [PDF]

				C. Sfagos, A. C Makis, A. Chaidos, E. C Hatzimichael, A. Dalamaga, K. Kosma, and K. L. Bourantas Serum ferritin, transferrin and soluble transferrin receptor levels in multiple sclerosis patients Multiple Sclerosis, June 1, 2005; 11(3): 272 - 275. [Abstract] [PDF]

				J. Imitola, M. Comabella, A. K. Chandraker, F. Dangond, M. H. Sayegh, E. Y. Snyder, and S. J. Khoury Neural Stem/Progenitor Cells Express Costimulatory Molecules That Are Differentially Regulated by Inflammatory and Apoptotic Stimuli Am. J. Pathol., May 1, 2004; 164(5): 1615 - 1625. [Abstract] [Full Text] [PDF]

				I. Banisor and B. Kalman Bcl-2 and its homologues in the brain of patients with multiple sclerosis Multiple Sclerosis, April 1, 2004; 10(2): 176 - 181. [Abstract] [PDF]

				M. S. COOKE, M. D. EVANS, M. DIZDAROGLU, and J. LUNEC Oxidative DNA damage: mechanisms, mutation, and disease FASEB J, July 1, 2003; 17(10): 1195 - 1214. [Abstract] [Full Text] [PDF]

				P. J. De Bleser, G. Xu, K. Rombouts, V. Rogiers, and A. Geerts Glutathione Levels Discriminate between Oxidative Stress and Transforming Growth Factor-beta Signaling in Activated Rat Hepatic Stellate Cells J. Biol. Chem., November 26, 1999; 274(48): 33881 - 33887. [Abstract] [Full Text] [PDF]