Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice

Crit Care Med. 2013 May;41(5):1266-75. doi: 10.1097/CCM.0b013e31827711c9.


Objective: Hydrogen inhalation was neuroprotective in several brain injury models. Its mechanisms are believed to be related to antioxidative stress. We investigated the potential neurovascular protective effect of hydrogen inhalation especially effect on mast cell activation in a mouse model of intracerebral hemorrhage.

Design: Controlled in vivo laboratory study.

Setting: Animal research laboratory.

Subjects: One hundred seventy-one 8-week-old male CD-1 mice were used.

Interventions: Collagenase-induced intracerebral hemorrhage model in 8-week-old male CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation. The blood-brain barrier permeability and neurologic deficits were investigated at 24 and 72 hours after intracerebral hemorrhage. Mast cell activation was evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation on mast cell activation were confirmed in an autologous blood injection model intracerebral hemorrhage.

Measurement and main results: At 24 and 72 hours post intracerebral hemorrhage, animals showed blood-brain barrier disruption, brain edema, and neurologic deficits, accompanied with phosphorylation of Lyn kinase and release of tryptase, indicating mast cell activation. Hydrogen treatment diminished phosphorylation of Lyn kinase and release of tryptase, decreased accumulation and degranulation of mast cells, attenuated blood-brain barrier disruption, and improved neurobehavioral function.

Conclusion: Activation of mast cells following intracerebral hemorrhage contributed to increase of blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved blood-brain barrier disruption by prevention of mast cell activation after intracerebral hemorrhage.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Analysis of Variance
  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blotting, Western
  • Brain Edema / etiology
  • Brain Edema / pathology
  • Brain Edema / prevention & control
  • Brain Injuries / etiology
  • Brain Injuries / pathology
  • Brain Injuries / prevention & control*
  • Cell Movement / drug effects
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy*
  • Collagenases / pharmacology
  • Disease Models, Animal
  • Hydrogen / administration & dosage*
  • Hydrogen / pharmacokinetics
  • Hydrogen Peroxide / metabolism
  • Immunohistochemistry
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / physiology
  • Mice
  • Mice, Inbred Strains
  • Random Allocation
  • Reference Values
  • Survival Rate


  • Hydrogen
  • Hydrogen Peroxide
  • Collagenases