Ischemic intensity influences the distribution of delayed infarction and apoptotic cell death following transient focal cerebral ischemia in rats.
The aim of this study was to investigate whether the apoptotic process contributes to the delayed infarction that follows a middle cerebral artery (MCA) occlusion of 20 min (mild ischemia group) and to compare this with the delayed component of infarct following 2 h of MCA occlusion (severe ischemia group). Adult male Sprague-Dawley rats underwent left MCA occlusion for either 20 min or 2 h and were reperfused for 12, 24 and 72 h. On 2,3,5-triphenyltetrazolium chloride-stained coronal sections, delayed infarction was observed to develop in the whole MCA territory after mild ischemia, and also in the frontoparietal cortex after severe ischemia. At 24 h after 20 min of MCA occlusion, characteristic apoptotic features, including chromatin condensation and apoptotic bodies were frequently observed by electron microscopy. In both ischemic groups, Hoechst 33342 staining showed typically condensed and fragmented nuclei in the area showing delayed infarction, where TdT-dUTP nick end labeling (TUNEL)-positive cells were also significantly increased. Caspase-3 activity was also found to be elevated 24 and 72 h after reperfusion and this peaked at 24 h in both groups. These findings suggest that ischemic severity may influence the distribution of delayed infarction, and that apoptosis is the underlying pathophysiologic mechanism.
Lee
Seung-Hoon
SH
Department of Neurology, College of Medicine, Seoul National University, Neuroscience Research Institute, Chongno-gu, Seoul, 110-744, South Korea.
Kim
Manho
M
Kim
Young-Ju
YJ
Kim
Young-A
YA
Chi
Je-Geun
JG
Roh
Jae-Kyu
JK
Yoon
Byung-Woo
BW
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001562:Benzimidazoles; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D020768:Middle Cerebral Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013194:Staining and Labeling; D013997:Time Factors
D001562:Benzimidazoles; C447680:hoechst 32258; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases