HISTOCHEMICAL-DEMONSTRATION OF FREE-RADICALS (H2O2) IN ISCHEMIC BRAINEDEMA AND PROTECTIVE EFFECTS OF HUMAN RECOMBINANT SUPEROXIDE-DISMUTASE ON ISCHEMIC NEURONAL DAMAGE

A new histofluorescence method by HPAA (p-hydroxyphenyl acetic acid) f or free radicals in the brain tissue was devised to study neuronal dam age induced by ischemia. Cerebral ischemia was produced in rats by inj ection of plastic microspheres and arachidonic acid (AA) into the righ t carotid artery. The concentration of malondialdehyde (MDA; free radi cal) in cerebral cortex of aminotriazol (an H2O2-dependent inhibitor o f catalase) treated rats 2 h after stroke was 6.33 times the level bef ore infarction, while the concentration of MDA in h-r SOD (free radica l-scavenging enzyme) treated rats 2 h after stroke was significantly l ower than in untreated rats. The histochemical findings demonstrated m arked H2O2 production around blood vessels occluded by microspheres in the cerebral cortex of the aminotriazole treated rats 2 h after strok e together with disruption of the BBB. Light microscopical findings de monstrated extensive edematous changes in the aminotriazole treated ra ts 2 h after stroke, while pathological damage in SOD treated rat brai ns was absent or minimal. We conclude that free radicals are formed du ring ischemia, and that AA appears to be a major source of activated o xygen radicals. The findings indicate that SOD is protective against i schemia-induced neuronal damage.