Histochemical demonstration of free radicals (H2O2) in ischemic brain edema and protective effects of human recombinant superoxide dismutase on ischemic neuronal damage.
A new histofluorescence method by HPAA (p-hydroxyphenyl acetic acid) for free radicals in the brain tissue was devised to study neuronal damage induced by ischemia. Cerebral ischemia was produced in rats by injection of plastic microspheres and arachidonic acid (AA) into the right carotid artery. The concentration of malondialdehyde (MDA; free radical) in cerebral cortex of aminotriazol (an H2O2-dependent inhibitor of catalase) treated rats 2 h after stroke was 6.33 times the level before infarction, while the concentration of MDA in h-r SOD (free radical-scavenging enzyme) treated rats 2 h after stroke was significantly lower than in untreated rats. The histochemical findings demonstrated marked H2O2 production around blood vessels occluded by microspheres in the cerebral cortex of the aminotriazole treated rats 2 h after stroke together with disruption of the BBB. Light microscopical findings demonstrated extensive edematous changes in the aminotriazole treated rats 2 h after stroke, while pathological damage in SOD treated rat brains was absent or minimal. We conclude that free radicals are formed during ischemia, and that AA appears to be a major source of activated oxygen radicals. The findings indicate that SOD is protective against ischemia-induced neuronal damage.
Department of Neurological Surgery, Bizen City Hospital, Okayama, Japan.
H
H
Morooka
N
N
Hirotsune
T
T
Wani
T
T
Ohmoto
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001929:Brain Edema / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009410:Nerve Degeneration / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology*
D005609:Free Radicals; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase