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Oxidative DNA damage in the spinal cord in multiple sclerosis
Author(s) -
Abedin K. J.,
Papadopoulos D.,
Dexter D. T.,
Reynolds R.
Publication year - 2002
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2002.39286_53.x
Subject(s) - multiple sclerosis , spinal cord , pathology , central nervous system , dna damage , myelin , lesion , white matter , biology , immunology , medicine , dna , endocrinology , biochemistry , neuroscience , radiology , magnetic resonance imaging
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by multifocal demyelination and axonal loss. In addition to the role of the immune response in targeting oligodendrocytes and myelin in MS lesions, the extensive inflammatory infiltration is likely to lead to free radical production and oxidative damage to both oligodendrocytes/myelin and neurons. In this study we investigated the extent of free radical damage to DNA in postmortem MS spinal cord. Materials and methods: Serial 10 µm tissue sections were cut from 26 fixed and cryoprotected spinal cord blocks from 11 MS cases (age 64 ± 4 years, pmd 13 ± 2 h) and two controls (age 70 ± 9 years, pmd 22 ± 4 h). Lesions were characterized using H&E and LFB‐PAS histology and HLA‐DR immunohistochemistry. DNA oxidative damage was detected using a monoclonal antibody against 8‐hydroxy‐2′‐deoxyguanosine (8OHdG; supplied by Dr S Toyokuni, Kyoto), the most abundant modified DNA base. Results: Quantitative analysis revealed a 150% increase in 8OHdG+ cells relative to normal appearing WM and a 400% increase relative to control WM. A positive correlation was found between the level of macrophage infiltration (HLA‐DR+) and 8OHdG‐expressing cells. Discussion: These results suggest a role for oxidative damage to DNA due to free radicals in the evolution of the MS lesion.