Angiogenesis contributes to the neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats

Int J Neurosci. 2015;125(8):625-34. doi: 10.3109/00207454.2014.956101. Epub 2014 Sep 17.


Ischemic stroke is one of the leading causes of mortality and disability worldwide. Previous studies have indicated that hyperbaric oxygen preconditioning (HBO-PC) can induce neuroprotection against focal cerebral ischemia. However, the underlying mechanisms are still not fully understood, and the optimal regimen for preconditioning must be confirmed. In the present study, we designed eight preconditioning regimens and compared their neuroprotective effects. Hyperbaric oxygen preconditioning every other day for there sessions exhibited the best neuroprotective effect; the infarct volume was reduced by almost 50% at 48 h after middle cerebral artery occlusion. We also found that HBO-PC significantly increased the microvessel density and the CD31-positive cells in the penumbra at 72 h after stroke. These results indicate that angiogenesis is involved in the neuroprotection induced by HBO-PC. Moreover, we explored the roles of HIF-1α and angiogenic factors in the angiogenesis process induced by HBO-PC. The results from western blotting demonstrated that protein expression of Ang-2 in the HBO-PC group was significantly increased. In conclusion, HBO-PC reduced brain injury and improved neurological function after focal cerebral ischemia, as partly mediated by the increased microvessel density in the penumbra, and this effect may result from the upregulation of Ang-2.

Keywords: angiogenesis; angiopoietin-2; hyperbaric oxygen preconditioning; neuroprotection; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / prevention & control*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Hyperbaric Oxygenation / methods*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ischemic Preconditioning*
  • Male
  • Neovascularization, Physiologic / physiology*
  • Neurologic Examination
  • Neuroprotection / physiology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • von Willebrand Factor / metabolism


  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Platelet Endothelial Cell Adhesion Molecule-1
  • von Willebrand Factor