Axonal damage and oxidative stress during chronic experimental allergic encephalomyelitis

Abstract

ObjectivesIn the chronic disabling disease multiple sclerosis (MS), migration of monocytes across the blood-brain barrier is a crucial step in the formation of lesions in the central nervous system (CNS). Here we investigate whether infiltrating monocyte-derived macrophages contribute to axonal demyelination and damage by the secretion of oxygen radicals in chronic experimental allergic encephalomyelitis (EAE), the animal model for MS.MethodologyChronic EAE was induced in Dark Agouti rats and animals were sacrificed at various time points. Axonal damage and oxygen radicals were detected by immunohistochemistry for the accumulation of amyloid precursor protein (APP) and dephosphorylated neurofilament and nitrotyrosine, respectively. Chronic EAE animals were treated with luteolin, a naturally occurring dietary anti-oxidant, to study the involvement of oxygen radicals in the course of the disease. ResultsAxonal damage, as demonstrated by amyloid precursor protein accumulation and dephosphorylation of neurofilaments, is evident in both early and late stages of chronic EAE. Axonal damage was abundant in macrophage-infiltrated areas of the CNS of diseased animals. Luteolin treatment reduced cellular infiltration, oxidative stress as detected by nitrotyrosine levels and axonal damage in the CNS of EAE animals. ConclusionThese data suggest that macrophages contribute to axonal damage in EAE and that anti-oxidants may have a protective role in CNS inflammation and axonal damage as observed in MS and EAE