Inhalation of hydrogen gas attenuates cognitive impairment in transient cerebral ischemia via inhibition of oxidative stress

Neurol Res. 2012 Mar;34(2):187-94. doi: 10.1179/1743132812Y.0000000002. Epub 2012 Feb 2.


Objective: To investigate the effects of inhalation of hydrogen gas on cognitive impairment induced by transient cerebral ischemia and its potential mechanism.

Methods: Two-vessel occlusion rat model was used to produce 10-minute transient global cerebral ischemia. One hundred and twenty male Wistar rats were randomly divided into sham, sham+H(2), ischemia, and ischemia+H(2) groups (n = 30 each group). Inhalation of 2% hydrogen gas was performed immediately at the end of operation and lasted for 3 hours. Cognitive function of rats was evaluated via Morris water maze. Neuronal damage in the CA1 region was quantified according to their morphological changes revealed by hematoxylin-eosin staining. The levels of oxidative stress products malondialdehyde (MDA) and 8-iso-prostaglandin F2alpha, and the activities of anti-oxidative enzymes catalase and superoxide dismutase were measured to investigate the effects of inhalation of hydrogen gas on oxidative stress.

Results: Inhalation of hydrogen gas decreased significantly the average latency of the ischemic rats in finding hidden platform and elongated markedly their retention in the target quadrant. The neuronal density 3·3±2·1 cells/mm in CA1 region of the ischemic rats increased to 21·7±2·6 cells/mm after they were treated with hydrogen gas. Moreover, hydrogen gas made higher levels of MDA and 8-iso-PGF2α in the ischemic rats attenuate to 3·2±0·2, 3·5±0·5, 3·4±0·3 and 26·4±2·3, 28·2±2·6, 26·8±2·1 at reperfusion 4, 24, and 72 hours, respectively (P<0·01 versus ischemia group at each indicated time). By contrast, the activities of superoxide dismutase and catalase damaged by ischemia/reperfusion recovered to 129·7±14·8, 100·5±12·2 and 11·4±0·8, 9·6±1·1 at reperfusion 24 and 72 hours, respectively (P<0·01 versus ischemia group at each indicated time).

Conclusion: Inhalation of hydrogen gas could attenuate cognitive impairment in the ischemic rats. This protection is associated with decreased neuronal death in CA1 region and inhibition of oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • CA1 Region, Hippocampal / pathology*
  • Cognition Disorders / etiology
  • Cognition Disorders / prevention & control*
  • Disease Models, Animal
  • Hydrogen / pharmacology*
  • Ischemic Attack, Transient / complications*
  • Ischemic Attack, Transient / pathology
  • Male
  • Maze Learning / drug effects
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar


  • Antioxidants
  • Hydrogen