OXIDATIVE DAMAGE TO DNA IN PLAQUES OF MS BRAINS

A major cause of clinical disability in multiple sclerosis (MS) is rel ated to a degenerative process in the central nervous system (CNS) whi ch ultimately develops from a potentially reversible inflammation and demyelination. The mechanism of this degenerative process within MS le sions is not completely understood. We hypothesize that oxidative dama ge to DNA secondary to inflammation may contribute to irreversible tis sue alterations in a plaque. To test this assumption, we determined th e level of a DNA oxidative marker, 8-hydroxy-deoxy-guanosine (8-OH-dG) in the normal appearing white matter (NAWM), Plaque and cortical regi ons of cerebella from MS patients who suffered from severe cerebellar symptoms during the course of the disease, and in NAWM and cortical re gions of cerebella from non-neurological controls. We found a signific ant increase in DNA oxidation within plaques compared to NAWM specimen s in MS cerebella. A tendency for increase of oxidative markers in nor mal 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 loca ted in the proximity of these lesions is likely related to the release of reactive oxygen species (ROS) and nitric oxide (NO) during inflamm ation in the brain. This biochemical impairment of DNA and of other ma cromolecules may contribute to the development of severe clinical disa bility through the induction of degenerative changes within and outsid e of plaques in MS brains.