Antioxidant compounds EGB-761 and BN-52021 attenuate brain edema formation and hemeoxygenase expression following hyperthermic brain injury in the rat.
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.
Sharma
H S
HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden. Sharma@medcellbiol.uu.se
Drieu
K
K
Westman
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D001930:Brain Injuries / Q000150:complications* / Q000209:etiology; D002199:Capillary Permeability / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D005334:Fever / Q000150:complications*; D020441:Ginkgo biloba; D046934:Ginkgolides; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006358:Hot Temperature; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D000096983:Ginkgo Extract
D000975:Antioxidants; D004224:Diterpenes; D046934:Ginkgolides; D006419:Heme Oxygenase (Decyclizing); D007783:Lactones; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C045856:ginkgolide B; C105245:heme oxygenase-2