title: Focal and diffuse cortical degenerative changes in a marmoset model of multiple sclerosis.
abstract: BACKGROUND
  Degenerative features, such as neuronal, glial, synaptic and axonal loss, have been identified in neocortical and other grey matter structures in patients with multiple sclerosis, but mechanisms for neurodegeneration are unclear. Cortical demyelinating lesions are a potential cause of this degeneration, but the pathological and clinical significance of these lesions is uncertain as they remain difficult to identify and study in vivo. In this study we aimed to describe and quantify cellular and subcellular pathology in the cortex of myelin oligodendrocyte glycoprotein-induced marmoset experimental autoimmune encephalomyelitis using quantitative immunohistochemical methods.
  
  
  RESULTS
  We found evidence of diffuse axonal damage occurring throughout cortical grey matter with evidence for synaptic loss and gliosis and a 13.6% decrease in neuronal size and occurring in deep cortical layers. Evidence of additional axonal damage and a 29.6-36.5% loss of oligodendrocytes was found in demyelinated cortical lesions. Leucocortical lesions also showed neuronal loss of 22.2% and a 15.8% increase in oligodendrocyte size.
  
  
  CONCLUSIONS
  The marmoset experimental autoimmune encephalomyelitis model, therefore, shows both focal and generalized neurodegeneration. The generalized changes cannot be directly related to focal lesions, suggesting that they are either a consequence of diffusible inflammatory factors or secondary to remote lesions acting through trans-synaptic or retrograde degeneration.
authors.affiliation: Department of Clinical Neurology, University of Oxford, Oxford, UK. ian.pomeroy@nhs.net
authors.forename: I M
authors.initials: IM
authors.lastname: Pomeroy
authors.forename: E K
authors.initials: EK
authors.lastname: Jordan
authors.forename: J A
authors.initials: JA
authors.lastname: Frank
authors.forename: P M
authors.initials: PM
authors.lastname: Matthews
authors.forename: M M
authors.initials: MM
authors.lastname: Esiri
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D002144:Callithrix; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D007150:Immunohistochemistry; D009103:Multiple Sclerosis / Q000473:pathology*; D009410:Nerve Degeneration / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology