Hydrogen Peroxide Localization in Experimental Optic Neuritis

• The association of reactive oxygen species to altered permeability of the blood-brain barrier in acute experimental encephalomyelitis was investigated by ultrastructural cytochemical localization of hydrogen peroxide (H₂O₂) to sites in the optic nerve previously identified by extravasation of intravascular horseradish peroxidase. Using a modified cerium method, we found electron-dense cerium-derived H₂O₂ reaction product was localized to the perivascular space at the lamina retinalis, lamina choroidalis, and lamina scleralis. In the optic nerve head, electron-dense reaction product was observed in the presence of intravascular leukocytes, although adjacent perivascular and interstitial inflammatory cells at this site were scant. In the myelinated retrobulbar optic nerve, cerium-derived H₂O₂ reaction product was seen in the intravascular space of blood vessels and surrounding perivascular and interstitial foci of inflammatory cells. Reaction product was also observed in the extracellular space adjacent to the plasmalemma of axons and glial cells in the optic nerve head and retrobulbar nerve. The perivascular and intravascular distribution of cerium-derived reaction product suggests that H₂O₂ may play a role in the pathogenesis of altered vascular permeability in experimental optic neuritis and supports our previous observations of suppression of blood-brain barrier permeability by detoxification of H₂O₂ with the exogenous administration of antioxidant enzymes.