Oxidative Stress and Lymphocyte Alterations in Chronic Relapsing Experimental Allergic Encephalomyelitis in the Rat Hippocampus and Protective Effects of an Ethanolamine Phosphate Salt

Mol Neurobiol. 2020 Feb;57(2):860-878. doi: 10.1007/s12035-019-01774-8. Epub 2019 Sep 10.

Abstract

Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) exhibits neuropathological and immunological dysfunctions similar to those found in multiple sclerosis (MS) and has been used as an animal model of MS. Inflammatory infiltrates and oxidative stress have been linked to the development of both diseases. Ethanolamine plasmalogen derivates have been shown to be powerful antioxidants and immunomodulators. Therefore, the objective of this study was to analyse inflammatory infiltrates, the state of the oxidative defences and the possible protective effects of calcium, magnesium and phosphate ethanolamine (EAP) in the CR-EAE rat hippocampus. To this aim, we evaluated, by immunohistochemistry, T cell infiltrates, Iba-1+ (a marker of activated microglia) immunoreactivity and TUNEL (+) cells. We also measured the protein levels and activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR). In addition, reduced (GSH) and oxidized (GSSG) glutathione levels, lipid peroxidation and cholesterol as well as desmosterol content were determined. We found an increase in T cell infiltrates and Iba1+ immunoreactivity, lipid peroxidation, SOD, GP and GR activities as well as enhanced cholesterol levels and a decrease in CAT activity, GSH and desmosterol levels in the first and second attack in the CR-EAE rat hippocampus. Pretreatment of CR-EAE rats with EAP led to a delay in the onset of the clinical signs of the disease as well as a decrease in inflammatory infiltrates and alterations of the antioxidant defences in the hippocampus. Altogether, the present results suggest a protective role of EAP in the CR-EAE rat hippocampus.

Keywords: Antioxidant defences; CR-EAE; Ethanolamine phosphate; Hippocampus; Multiple sclerosis; Oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • CD3 Complex / metabolism
  • Catalase / metabolism
  • Chronic Disease
  • Encephalomyelitis, Autoimmune, Experimental / enzymology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Ethanolamines / pharmacology
  • Ethanolamines / therapeutic use*
  • Feeding Behavior / drug effects
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Hippocampus / pathology*
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Lipid Peroxidation / drug effects
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress* / drug effects
  • Rats, Inbred Lew
  • Rats, Wistar
  • Recurrence
  • Sterols / metabolism
  • Superoxide Dismutase / metabolism
  • Time Factors

Substances

  • CD3 Complex
  • Ethanolamines
  • Neuroprotective Agents
  • Sterols
  • phosphorylethanolamine
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glutathione