DIFFERENCES IN DNA FRAGMENTATION FOLLOWING TRANSIENT CEREBRAL OR DECAPITATION ISCHEMIA IN RATS

被引:107
作者
MACMANUS, JP [1 ]
HILL, IE [1 ]
PRESTON, E [1 ]
RASQUINHA, I [1 ]
WALKER, T [1 ]
BUCHAN, AM [1 ]
机构
[1] UNIV OTTAWA,OTTAWA,ON,CANADA
关键词
APOPTOSIS; DECAPITATION; DNA FRAGMENTATION; ISCHEMIA; NECROSIS; STROKE;
D O I
10.1038/jcbfm.1995.93
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The time course of appearance of cells with DNA damage was studied in rats following transient severe forebrain ischemia. This DNA damage could be detected by in situ end-labeling on brain sections. The breaks in DNA appeared selectively by day 1 in the striatum and later in the CAL region of the hippocampus. It was possible by double labeling to show that there was no DNA damage in astrocytes. The DNA breaks consisted of laddered DNA fragments indicative of an ordered apoptotic type of internucleosomal cleavage, which persisted without smearing for up to 7 days of reperfusion. In contrast, the DNA breaks following ischemia induced by decapitation were random and, after gel electrophoresis, consisted of smeared fragments of multiple sizes. There was some early regional cellular death, restricted to the dentate of the hippocampus, prior to the pannecrotic degeneration. It is concluded that transient forebrain ischemia leads to a type of neuronal destruction that is not random necrosis but that shares some component of the apoptotic cell death pathway.
引用
收藏
页码:728 / 737
页数:10
相关论文
共 55 条
[1]  
An G., Lin T.N., Liu J.S., Xue J.J., He Y.Y., Hsu C.Y., Expression of c-fos and c-jun family genes after focal cerebral ischemia, Ann Neurol, 33, pp. 457-464, (1993)
[2]  
Araki T., Kato H., Inoue T., Kogure K., Regional impairment of protein synthesis following brief cerebral ischemia in the gerbil, Acta Neuropathol, 79, pp. 501-505, (1990)
[3]  
Auer R.N., Wieloch T., Olsson Y., Siesjo B.K., The distribution of hypoglycemic brain damage, Acta Neuropathol, 64, pp. 177-191, (1984)
[4]  
Buja L.M., Eigenbrodt M.L., Eigenbrodt E.H., Apoptosis and necrosis: Basic types and mechanisms of cell death, Arch Pathol Lab Med, 117, pp. 1208-1214, (1993)
[5]  
Chopp M., Li Y., Zhang Z.G., Freytag S.O., p53 Expression in brain after middle cerebral artery occlusion in the rat, Biochem Biophys Res Commun, 182, pp. 1201-1207, (1992)
[6]  
Clarke P.G.H., Developmental cell death: Morphological diversity and multiple mechanisms, Anat Embryol, 181, pp. 195-213, (1990)
[7]  
Deckworth T.L., Johnson E.M., Temporal analysis of events associated with programmed cell death (apoptosis) of sympathetic neurons deprived of nerve growth factor, J Cell Biol, 123, pp. 1207-1222, (1993)
[8]  
Dempsey R.J., Carney J.M., Kindy M.S., Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain, J Cereb Blood Flow Metab, 11, pp. 979-985, (1991)
[9]  
Deshpande J., Bergstedt K., Linden T., Kalimo H., Wieloch T., Ultrastructural changes in the hippocampus CA1 region following transient cerebral ischemia: Evidence against programmed cell death, Exp Brain Res, 88, pp. 91-105, (1992)
[10]  
Diana A., Setzu M., Sirigu S., Diaz G., Nuclear patterns of apoptotic and developing neurons of superior cervical ganglion of newborn rat, Int J Devl Neurosci, 11, pp. 773-780, (1993)