Antioxidant compounds EGB-761 and BN-52021 attenuate brain edema formation and hemeoxygenase expression following hyperthermic brain injury in the rat

Acta Neurochir Suppl. 2003;86:313-9. doi: 10.1007/978-3-7091-0651-8_68.


Role of carbon monoxide (CO) in hyperthermic brain injury induced brain pathology was examined in a rat model using immunohistochemistry of the hemeoxygenase-2 (HO-2) enzyme. Exposure of rats to 4 h heat stress at 38 degrees C resulted in profound hyperthermia, breakdown of the blood-brain barrier (BBB), brain edema formation, cell damage and expression of HO-2 in several brain regions. Pretreatment with potent antioxidant compounds EGB-761 and BN-52021 markedly reduced the HO-2 expression, BBB breakdown, brain edema formation and cell damage without attenuating the hyperthermic response. This effect was most marked in animals treated with EGB-761. These observations suggest that upregulation of HO-2 representing generation of CO plays important roles in hyperthermic brain injury, and oxidative stress seems to be one of the most important signals in inducing HO-2 expression in hyperthermia, not reported earlier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Blood-Brain Barrier / drug effects
  • Brain Edema / etiology
  • Brain Edema / prevention & control*
  • Brain Injuries / complications*
  • Brain Injuries / etiology
  • Capillary Permeability / drug effects
  • Diterpenes / pharmacology*
  • Fever / complications*
  • Ginkgo biloba
  • Ginkgolides
  • Heme Oxygenase (Decyclizing) / antagonists & inhibitors*
  • Hot Temperature
  • Lactones / pharmacology*
  • Male
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / etiology
  • Stress, Physiological / pathology
  • Stress, Physiological / physiopathology


  • Antioxidants
  • Diterpenes
  • Ginkgolides
  • Lactones
  • Plant Extracts
  • Ginkgo biloba extract
  • ginkgolide B
  • Heme Oxygenase (Decyclizing)
  • heme oxygenase-2