Molecular hydrogen suppresses reactive astrogliosis related to oxidative injury during spinal cord injury in rats

CNS Neurosci Ther. 2014 Aug;20(8):778-86. doi: 10.1111/cns.12258. Epub 2014 Mar 31.


Aims: Spinal cord injury (SCI) can induce excessive astrocyte activation. Hydrogen has been deemed as a novel antioxidant. We investigated whether molecular hydrogen could act as an antiastrogliosis agent during SCI and oxidative injury in experimental rats and cultured astrocytes.

Methods: Hydrogen-rich saline (HS, 8 mL/kg, i.p.) was injected every 12 h after SCI in rats. The expression of STAT3, p-STAT3, and glial fibrillary acidic protein (GFAP); the release of IL-1β, IL-6, and TNF-α; and astrogliosis, along with the BBB score, were evaluated. Culturing astrocytes with hydrogen-rich medium, the intracellular reactive oxygen species (ROS), astrogliosis, and the release of proinflammatory cytokines were assessed after H2O2-induced injury.

Results: In the HS group, the expression of STAT3, p-STAT3, and GFAP and the proinflammatory cytokines were decreased in local spinal cord on postoperation day (POD) 3; on PODs 7 and 14, reactive astrogliosis was suppressed, and the locomotor function was also improved. Furthermore, hydrogen-rich medium attenuated the intracellular production of ROS (especially HO•), astrogliosis, and the secretion of proinflammatory cytokines in astrocytes 12 h after H2O2-induced injury.

Conclusions: Molecular hydrogen could suppress reactive astrogliosis after contusive SCI and reduce the release of proinflammatory cytokines produced by active astrocytes related to oxidative injury. Thus, molecular hydrogen is potential to be a neuroprotective agent.

Keywords: Astrogliosis; Glial scar; Hydrogen; Oxidative injury; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chlorides / pharmacology
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Ferric Compounds / pharmacology
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / chemically induced*
  • Hydrogen / pharmacology*
  • Hydrogen Peroxide / toxicity
  • Locomotion / drug effects
  • Lower Extremity / physiopathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • STAT Transcription Factors / metabolism
  • Spinal Cord Injuries / complications*
  • Spinal Cord Injuries / pathology*


  • Chlorides
  • Cytokines
  • Ferric Compounds
  • Glial Fibrillary Acidic Protein
  • STAT Transcription Factors
  • Hydrogen
  • Hydrogen Peroxide
  • ferric chloride