Spinal Cord Neuropathology in Rat Experimental Autoimmune Encephalomyelitis

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) in which clinical neurological signs and histopathologic changes of disease can be suppressed by feeding CNS myelin proteins. Using immunohistochemistry and image analysis, the cellular immune response was quantified over the rostral-caudal axis of the spinal cord in rats with EAE and in animals fed high- or low-dose myelin basic protein (MBP) prior to inducing EAE (tolerized animals). In a subset of rats, MBP was fed 9 days after MBP immunization to examine the effect of oral tolerance on the progression of CNS pathology. In unfed rats or rats fed vehicle only, activated microglia and macrophages were co-localized with T-lymphocytes throughout the spinal cord, but greater cellular reactions were evident in gray matter relative to white matter. In all tolerized animals, the CNS inflammatory response was reduced relative to controls. Subtle pathologic changes were occasionally observed in the CNS of MBP-fed animals, but the distribution of inflammatory cells in the dorso-ventral axis was more polarized in animals fed high-dose MBP. In this group, more T-cells and activated microglia were present in the dorsal spinal cord, specifically in the gray matter. In the group fed MBP after disease induction, clinical disease progressed as in control non-fed rats, but recovery from disease appeared to be accelerated. Thus, the results presented here provide a comprehensive analysis of the distribution and magnitude of inflammatory cells within the spinal cord in EAE and challenge the theory that MBP-induced EAE is only a white matter disease. These data also describe how the activation and distribution of immune effector cells is altered by oral tolerance and may help predict a range of neurological deficits not previously appreciated in EAE, particularly those effected by gray matter pathology.