DNA cleavage and proteolysis of microtubule-associated protein 2 after cerebral ischemia of different severity.
We report temporal profiles of cytoplasmic proteolysis and genomic DNA cleavage after cerebral ischemia of different severity in gerbils. Global forebrain ischemia by bilateral common carotid artery occlusion for 5 min with reperfusion, severe unilateral hemispheric ischemia by unilateral common carotid artery occlusion for 30 min with reperfusion, and complete ischemia by decapitation were used. The hippocampus was examined for proteolysis by using immunohistochemistry for microtubule-associated protein 2, DNA cleavage by using in situ nick-end labelling, and nuclear morphology by Hematoxylin staining. During evolution of delayed neuronal death after transient forebrain ischemia, loss of the immunoreaction for microtubule-associated protein 2 occurred almost in parallel with DNA cleavage in the CA1 region. In contrast, disappearance of the immunoreaction for microtubule-associated protein 2 was much faster than genomic DNA cleavage after unilateral hemispheric ischemia and reperfusion. The microtubule-associated protein 2 immunoreactivity was completely lost before development of changes in nuclear morphology or DNA cleavage after complete ischemia. The present study demonstrated the differences between necrosis and delayed neuronal death, but the nuclear morphology in the latter was not exactly the same as seen in apoptosis. Some elements of both necrotic and apoptotic machineries may work following transient ischemia, and the degree of ischemic insult may determine the character of cell death process.
Yagita
Y
Y
First Department of Medicine, Osaka University School of Medicine, Japan.
Matsumoto
M
M
Kitagawa
K
K
Mabuchi
T
T
Ohtsuki
T
T
Hori
M
M
Yanagihara
T
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000502:physiology; D002467:Cell Nucleus / Q000648:ultrastructure; D004249:DNA Damage; D005849:Gerbillinae; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology; D013997:Time Factors
D008869:Microtubule-Associated Proteins