Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death.
We investigated the pathogenic role of free radical formation in ischemic neuronal death using radical scavenger, superoxide dismutase. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. The effects of free superoxide dismutase and a derivatized superoxide dismutase, pyran copolymer conjugated superoxide dismutase, on early ischemic damages, detected sensitively by the immunohistochemical reaction for microtubule associated protein 2, and a subsequent delayed neuronal death after restoration of blood flow were investigated. Preischemic treatment by pyran conjugated superoxide dismutase showed clear protective effects against both the neuronal damages detected by immunohistochemistry after 5 min ischemia and the delayed neuronal necrosis after one week of recovery, although no clear beneficial effects were observed when this drug was administered just before the recirculation or free superoxide dismutase was used. These results strongly suggest that free radical generation during brief period of ischemia plays a pivotal role in triggering the ischemic neuronal damages causing delayed neuronal death at the selectively vulnerable areas of the brain.
First Department of Internal Medicine, School of Medicine, Osaka University, Japan.
K
K
Kitagawa
M
M
Matsumoto
T
T
Oda
M
M
Niinobe
R
R
Hata
N
N
Handa
R
R
Fukunaga
Y
Y
Isaka
K
K
Kimura
H
H
Maeda
D000818:Animals; D002470:Cell Survival; D005260:Female; D005609:Free Radicals; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D011712:Pyramidal Tracts / Q000473:pathology / Q000503:physiopathology; D012016:Reference Values; D013482:Superoxide Dismutase / Q000378:metabolism*
D005609:Free Radicals; D013482:Superoxide Dismutase