Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model

Neurotherapeutics. 2017 Jan;14(1):199-211. doi: 10.1007/s13311-016-0480-0.

Abstract

Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord. For this purpose, samples obtained from EAE rats and relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the clinical variables of the disease, i.e. oxidative damage and LBP, were established. Although the conclusions of this research are indeed relevant, further investigation would be necessary to establish the intrinsic mechanisms of the MS-oxidative stress-microbiota relationship.

Keywords: Dimethyl fumarate; Experimental autoimmune encephalomyelitis; Lipopolysaccharide binding protein; Natalizumab; Oxidative stress; Relapsing-remitting multiple sclerosis.

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acute-Phase Proteins / metabolism*
  • Adult
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Cell Count
  • Dasyproctidae
  • Dimethyl Fumarate / administration & dosage
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Female
  • Humans
  • Lipid Peroxidation
  • Lipopolysaccharides / metabolism
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Multiple Sclerosis / metabolism*
  • Natalizumab / administration & dosage
  • Neurons / drug effects
  • Oxidative Stress*
  • Rats
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Natalizumab
  • lipopolysaccharide-binding protein
  • Dimethyl Fumarate
  • Acetylcysteine