Sublethal cerebral ischemia inhibits caspase-3 activation induced by subsequent prolonged ischemia in the C57Black/Crj6 strain mouse.
Caspase-3 activation has been implicated in ischemic neuronal death. In the present study, we examined if cerebral ischemic tolerance induced by sublethal ischemia is associated with an attenuation of caspase-3 activation in a mouse forebrain ischemia model. Forebrain ischemia in C57Black/Crj6 strain mice was induced by bilateral common carotid artery occlusion (BCCAO) for 18 min. Two episodes of 6-min ischemia were carried out as preconditioning 48 and 72 h before the 18-min BCCAO. Caspase-3-like activity was determined by fluorescently monitoring the release of amino-4-methylcoumarin from N-acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin in the striatal protein extracts at 4, 24, and 72 h after reperfusion. The results showed that the ischemic preconditioning significantly attenuated caspase-3 activation at 4, 24, and 72 h after reperfusion, and reduced neuronal loss caused by the 18-min ischemia as examined on the 7th day after reperfusion. The present results suggest that the neuroprotection achieved by ischemic preconditioning is related to an attenuation of caspase-3 activation.
Qi
S
S
Department of Anesthesiology, Niigata University Graduate School of Medicine, 1-757 Asahimachi, Niigata 951-8510, Japan. qshmail@med.niigata-u.ac.jp
Zhan
R Z
RZ
Wu
C
C
Fujihara
H
H
Yamakura
T
T
Baba
H
H
Taga
K
K
Shimoji
K
K
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D004789:Enzyme Activation; D019194:Ischemic Preconditioning; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D016548:Prosencephalon / Q000201:enzymology / Q000473:pathology; D015424:Reperfusion; D013997:Time Factors
D061945:Caspase Inhibitors; D003374:Coumarins; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C028743:7-amino-4-methylcoumarin