title: Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.
abstract: Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America; Department of Emergency Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Dohi
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, United States of America; Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Kraemer
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Erickson
authors.affiliation: Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States of America.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: McMillan
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, United States of America.
authors.forename: Andrej
authors.initials: A
authors.lastname: Kovac
authors.affiliation: Laboratory of Biomedical Microbiology and Immunology, Department of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy, Kosice, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Flachbartova
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, United States of America.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Hansen
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Saint Louis University School of Medicine, Edward A. Doisy Research Center, St. Louis, MO, United States of America.
authors.forename: Gul N
authors.initials: GN
authors.lastname: Shah
authors.affiliation: Opthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States of America.
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, United States of America.
authors.forename: Therese
authors.initials: T
authors.lastname: Salameh
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States of America; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, United States of America.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000097:blood; D060766:Drinking Water / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D060766:Drinking Water; D018696:Neuroprotective Agents; D006859:Hydrogen