Effect of hydrogen gas on the survival rate of mice following global cerebral ischemia

Shock. 2012 Jun;37(6):645-52. doi: 10.1097/SHK.0b013e31824ed57c.


Global cerebral ischemia and reperfusion (I/R) often result in high mortality. Free radicals have been reported to play an important role in global cerebral I/R, and therefore, reduction of these might improve the outcome. Here, we investigated the effect of hydrogen gas (H2) (a strong free radical scavenger) on the survival rate of mice following global cerebral I/R. We further examined the histopathological outcome and also the brain water content (as a possible determinant of mortality). Male C57BL/6J mice were subjected to global cerebral I/R by means of 45-min bilateral common carotid artery occlusion (BCCAO). A total of 160 mice were divided into three groups: sham surgery (sham group), BCCAO without H2 (BCCAO group), and BCCAO treated with 1.3% H2 (BCCAO + H2 group). We observed that H2 treatment significantly (P = 0.0232) improved the 7-day survival rate of mice, from 8.3% (BCCAO group, n = 12) to 50% (BCCAO + H2 group, n = 10). Histopathological analysis revealed that H2 treatment significantly attenuated neuronal injury and autophagy in the hippocampal cornu ammonis 1 sector and also brain edema, after 24 h of reperfusion. The beneficial effects of H2 treatment on brain injury were associated with significantly lower levels of oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) in the brain tissue. Thus, we believe that H2 may be an effective treatment for global cerebral I/R.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Administration, Inhalation
  • Animals
  • Body Water / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Capillary Permeability
  • Cerebrovascular Circulation
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Free Radical Scavengers / administration & dosage*
  • Free Radical Scavengers / therapeutic use
  • Hippocampus / pathology
  • Hydrogen / administration & dosage*
  • Hydrogen / therapeutic use
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Reperfusion Injury / mortality
  • Reperfusion Injury / pathology
  • Reperfusion Injury / therapy*
  • Serum Albumin / analysis
  • Survival Rate


  • Free Radical Scavengers
  • Microtubule-Associated Proteins
  • Serum Albumin
  • Malondialdehyde
  • Hydrogen
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine