Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischemia rat model

Brain Res. 2009 Feb 23:1256:129-37. doi: 10.1016/j.brainres.2008.11.048. Epub 2008 Nov 27.


Cerebral hypoxia-ischemia (HI) represents a major cause of brain damage in the term newborn. This study aimed to examine the short and long-term neuroprotective effect of hydrogen saline (H(2) saline) using an established neonatal HI rat pup model. Seven-day-old rat pups were subjected to left common carotid artery ligation and then 90 min hypoxia (8% oxygen at 37 degrees C). H(2) saturated saline was administered by peritoneal injection (5 ml/kg) immediately and again at 8 h after HI insult. At 24 h after HI, the pups were decapitated and brain morphological injury was assessed by 2,3,5-triphenyltetrazolium chloride (TTC), Nissl, and TUNEL staining. Acute cell death, inflammation and oxidative stress were evaluated at 24 h by studying caspase-3 activity, MDA measurement as well as Iba-1 immunochemistry in the brain. At 5 weeks after HI, spontaneous activity test and Morris water maze test were conducted. We observed that H(2) saline treatment reduced the caspase activity, MDA, Iba-1 levels, the infarct ratio, and improved the long-term neurological and neurobehavioral functions. H(2) saline has potentials in the clinical treatment of HI and other ischemia-related cerebral diseases.

MeSH terms

  • Animals
  • Animals, Newborn
  • Body Weight / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Calcium-Binding Proteins / metabolism
  • Caspase 3 / metabolism
  • Cell Death / drug effects
  • Disease Models, Animal
  • Hydrogen / administration & dosage
  • Hydrogen / therapeutic use*
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Inflammation / drug therapy
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Microfilament Proteins
  • Motor Activity / drug effects
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Posture / physiology
  • Rats
  • Recovery of Function / drug effects
  • Sodium Chloride / administration & dosage
  • Sodium Chloride / therapeutic use*


  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Neuroprotective Agents
  • Sodium Chloride
  • Malondialdehyde
  • Hydrogen
  • Casp3 protein, rat
  • Caspase 3