The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia

Neurobiol Dis. 2008 Jan;29(1):1-13. doi: 10.1016/j.nbd.2007.07.020. Epub 2007 Jul 28.


We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague-Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 min of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Annexin A5 / metabolism
  • Apoptosis / physiology*
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain / pathology*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Caspase 3 / metabolism
  • Cell Count / methods
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gait Disorders, Neurologic / etiology
  • Hyperbaric Oxygenation*
  • In Situ Nick-End Labeling / methods
  • Ischemic Attack, Transient / complications
  • Ischemic Attack, Transient / mortality
  • Ischemic Attack, Transient / pathology*
  • Ischemic Attack, Transient / prevention & control
  • Ischemic Preconditioning / methods*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Time Factors


  • Annexin A5
  • Brain-Derived Neurotrophic Factor
  • Caspase 3