Overexpression of CuZn-superoxide dismutase reduces hippocampal injury after global ischemia in transgenic mice.
OBJECTIVE
The role of copper, zinc-superoxide dismutase (CuZn-SOD) in hippocampal injury after transient global ischemia was studied using transgenic (Tg) mice and wild-type littermates.


METHODS
Global ischemia was induced by bilateral common carotid artery occlusion. The hemisphere with the hypoplastic posterior communicating artery was determined and then the hippocampus in this hemisphere was evaluated qualitatively using a score of 0 to 4 and quantitatively using an image analyzer.


RESULTS
Hippocampal injury was reduced in Tg mice after both 5 and 10 minutes of ischemia. In the 5-minute ischemia group, the mean score of the injury was significantly lower in Tg than nontransgenic (nTg) mice at 3 days. In the 10-minute group, the hippocampal injury was reduced more in Tg than nTg mice at 1 day. Quantitative evaluation by an image analyzer confirmed the qualitative data. Neurons with fragmented DNA were also studied in the hippocampal injury. In the 5-minute group, despite the reduction of the injury in Tg mice, their neurons with fragmented DNA were relatively increased at 1 day. In the 10-minute group, this ratio was almost the same in both nTg and Tg mice.


CONCLUSIONS
CuZn-SOD plays a protective role in the pathogenesis of selective hippocampal injury after brief ischemia, whether the insult is relatively mild or intense. Furthermore, CuZn-SOD may reduce both necrotic and DNA fragmented neuronal death after global ischemia.
Murakami
K
K
Department of Neurological Surgery and Neurology, School of Medicine, University of California, San Francisco, USA.
Kondo
T
T
Epstein
C J
CJ
Chan
P H
PH
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology*; D053938:DNA Fragmentation; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*
D018696:Neuroprotective Agents; D013482:Superoxide Dismutase