Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model

Brain Res Bull. 2018 Sep;142:122-128. doi: 10.1016/j.brainresbull.2018.07.006. Epub 2018 Jul 18.


Objective: Hydrogen inhalation has been found to be neuroprotective and anti-oxidative in several brain injury models. Building on these studies, we investigated potential neuroprotective effects of hydrogen inhalation in a rat model of intracerebral hemorrhage (ICH), focusing on apoptosis and inflammation.

Methods: Forty-five 8-week-old male Sprague-Dawley rats were randomly divided into three groups (n = 15 per each group): a sham group, ICH group, and ICH + hydrogen group. Induction of ICH was performed via injection of 0.23 U of bacterial collagenase type IV into the left striatum. Hydrogen was administered via spontaneous inhalation. Mortality and neurologic deficits were investigated at 6, 24, and 48 h after ICH. To investigate the antioxidative activity of hydrogen gas, the expression of malondialdehyde was measured. Real-time polymerase chain reaction analyses of TNF-a, IL-1b, BDNF, and caspase-3 expression were used to detect anti-inflammatory and anti-apoptotic effects. Neuroprotective effect was evaluated by immunohistochemical and TUNEL staining.

Result: At 6, 24 and 48 h post-intracerebral hemorrhage, animals showed brain edema and neurologic deficits, accompanied by up-regulation of TNF-a, IL-b, BDNF, and caspase-3, which is indicative of neuroinflammation, neuroprotection, and apoptosis. Hydrogen treatment significantly reduced the level of oxidative stress, neuroinflammation, neuronal damage, and apoptosis-related genes. This was accompanied by increased neurogenesis and expression of growth factor-related genes at <24 h, but not 48 h, after ICH.

Conclusion: H2 gas administration exerted a neuroprotective effect against early brain injury after ICH through anti-inflammatory, neuroprotective, anti-apoptotic, and antioxidative activity.

Keywords: Apoptosis; Hydrogen; Intracerebral hemorrhage; Key words; Neuroprotection; Oxidative stress; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / pathology
  • Disease Models, Animal
  • Hydrogen / administration & dosage*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Male
  • Neuroprotective Agents / administration & dosage*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Random Allocation
  • Rats, Sprague-Dawley


  • Neuroprotective Agents
  • Hydrogen