title: Manipulation of Oxygen and Endoplasmic Reticulum Stress Factors as Possible Interventions for Treatment of Multiple Sclerosis: Evidence for and Against.
abstract: Multiple sclerosis (MS) is normally considered a chronic inflammatory disease of the central nervous system (CNS), where T-cells breaching the blood brain barrier react against proteins of the axonal myelin sheaths, leading to focal plaques and demyelination in the brain and spinal cord. Many current therapies are immunosuppressive in nature and are designed to target the immune system at an early stage of the disease. But there is no cure and MS may evolve into a neurodegenerative disease, where immunomodulatory treatments appear less effective. Neurodegeneration is influenced by oxidative and endoplasmic reticulum (ER) mediated stress which can be induced independently of immune processes. Since 1970, MS patients have been self-managing their long term symptoms using hyperbaric oxygen and reporting improvement in their symptoms, especially bladder control. In contrast, the majority of clinical trial evidence does not support the views of patients. Therefore does oxygen under pressure affect brain tissue by modulating oxidative or ER stress at the cellular level resulting in CNS tissue repair or deterioration? This chapter reviews our understanding and the role of oxidative and ER stress in the context of employing hyperoxia treatments to treat MS and evaluate its effects on neural cells.
authors.affiliation: St Luke's Campus, University of Exeter Medical School, Heavitree Road, EX1 2LU, Exeter, Devon, UK. p.eggleton@exeter.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Eggleton
authors.affiliation: DDRC Healthcare, Plymouth, UK.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Smerdon
authors.affiliation: St Luke's Campus, University of Exeter Medical School, Heavitree Road, EX1 2LU, Exeter, Devon, UK.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Holley
authors.affiliation: St Luke's Campus, University of Exeter Medical School, Heavitree Road, EX1 2LU, Exeter, Devon, UK.|Department of Neurology, Royal Devon & Exeter Hospital Foundation Trust, Exeter, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Gutowski
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000627:therapeutic use*
chemical_list: D010100:Oxygen
keywords: Autoimmunity; Hyperbaric oxygen; Myelin; Neurons; Oligodendrocytes; Unfolded protein response