A model of global cerebral ischemia in C57 BL/6 mice.
A reproducible model of global cerebral ischemia in mice is essential for elucidating the molecular mechanism of ischemic neuronal injury. Such a model is particularly important in the mouse because many genetically engineered mutant animals are available. In C57BL/6 and SV129/EMS mice, we evaluated a three-vessel occlusion model. Occlusion of the basilar artery with a miniature clip was followed by bilateral carotid occlusion. The mean cortical cerebral blood flow was reduced to less than 10% of the preischemic value, and the mean anoxic depolarization was attained within 1 minute. In C57BL/6 mice, there was CA1 hippocampal neuronal degeneration 4 days after ischemia. Neuronal damage depended upon ischemic duration: the surviving neuronal count was 78.5 +/- 8.5% after 8-minute ischemia and 8.4 +/- 12.7% after 14-minute ischemia. In SV129/EMS mice, similar neuronal degeneration was not observed after 14-minute ischemia. The global ischemia model in C57BL/6 mice showed high reproducibility and consistent neuronal injury in the CA1 sector, indicating that comparison of ischemic outcome between wild-type and mutant mice could provide meaningful data using the C57BL/6 genetic background. Strain differences in this study highlight the need for consideration of genetic background when evaluating ischemia experiments in mice.
Yonekura
Ichiro
I
Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan.
Kawahara
Nobutaka
N
Nakatomi
Hirofumi
H
Furuya
Kazuhide
K
Kirino
Takaaki
T
D000818:Animals; D001488:Basilar Artery / Q000033:anatomy & histology / Q000473:pathology / Q000601:surgery; D001831:Body Temperature; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D004594:Electrophysiology; D006439:Hemodynamics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012039:Regional Blood Flow; D013525:Surgical Instruments