Amelioration of hippocampal neuronal damage after global ischemia by neuronal overexpression of BCL-2 in transgenic mice.
OBJECTIVE
Reports suggesting the involvement of apoptosis in ischemic neuronal damage have been accumulating, and protection against apoptotic death by BCL-2 has been shown in many types of cells. Overexpression of BCL-2 has been shown to reduce infarct size after focal ischemia. The purpose of the present study was to assess whether BCL-2 exerted its effect on selective neuronal vulnerability after transient global ischemia.


METHODS
Transgenic mice overexpressing BCL-2 in neurons and their littermates were subjected to transient forebrain ischemia for 12 minutes, and the hippocampus was examined 7 days later with conventional histology, immunohistochemistry, and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of fragmented DNA.


RESULTS
Although both types of mice showed a similar degree of ischemic insult, transgenic mice showed a lesser degree of neuronal death together with DNA fragmentation in the hippocampus than their littermates.


CONCLUSIONS
Overexpression of BCL-2 in neurons mitigates selective neuronal vulnerability in the hippocampus of transgenic mice after transient global ischemia.
Kitagawa
K
K
Division of Strokology, First Department of Internal Medicine, Osaka University Medical, Osaka, Japan. kitagawa@medone.med.osaka-u.ac.jp
Matsumoto
M
M
Tsujimoto
Y
Y
Ohtsuki
T
T
Kuwabara
K
K
Matsushita
K
K
Yang
G
G
Tanabe
H
H
Martinou
J C
JC
Hori
M
M
Yanagihara
T
T
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D006624:Hippocampus / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2