BLOOD-BRAIN BARRIER DISRUPTION AND HYDROGEN PEROXIDE LOCALIZATION IN OPTIC NEURITIS: A CORRELATIVE MRI AND TEM STUDY
E. Ann Ellis¹, John R. Guy¹, Barbara L. Beck², and Jeffrey R. Fitzsimmons², Departments of Ophthalmology¹ and Radiology², College of Medicine, University of Florida, Gainesville, FL 32610

Optic neuritis, a demyelinating autoimmune disease and usually the initial presentation of multiple sclerosis (MS), is studied in the animal model, experimental allergic enephalomyelitis (EAE). Damage to the blood-brain barrier (BBB) and free radical derived oxidants, including hydrogen peroxide (H₂O₂), have been implicated in the pathology of EAE and other inflammatory diseases. Disruption of the BBB is monitored clinically in human cases by magnetic resonance imaging (MRI) of gadolinium-DTPA (Gd-DTPA) leakage. Optic nerves of guinea pigs sensitized to EAE were imaged by MRI (without and with Gd-DTPA) prior to euthanasia which was followed by cytochemical localization of H₂O₂ by the cerium NADH oxidase method. MRI showed no Gd-DTPA leakage in normal control optic nerves but there were variable sites of Gd-DTPA leakage in EAE optic nerves. H₂O₂ localized in the lumen, cell junctions, basement membrane and perivascular areas of endothelial cells of the subarachnoid space, choroid, optic nerve head, retrobulbar areas and on the plasmalemma of inflammatory cells of EAE optic nerves but not in normal optic nerves. The time course and sites of Gd-DTPA leakage are similar to those of cerium deposition and suggest that H₂O₂ plays a role in the pathology of BBB disruption in EAE.