title: Diabetes enhances apoptosis induced by cerebral ischemia.
abstract: The aim of this study is to explore the mechanism by which diabetes exaggerates cerebral stroke and its outcome. Since ischemia can be related to not only necrosis but apoptosis as well, we compared the development of apoptosis in STZ-diabetic rats and STZ-diabetic rats subjected to occlusion of the middle cerebral artery (MCA). 24-48 hr following MCA occlusion the animals were killed, the brain removed and prepared for evaluation by several indexes of apoptosis: nucleosomal DNA fragmentation, TUNEL staining, activation of caspase-3 and alteration in the expression of Bax and Bcl2. DNA fragmentation was not detected in the cortex of normal and diabetic animals, but was evident following MCA occlusion in diabetic rats. Bax expression was increased in the cortex of normal rats following MCA occlusion and this expression was further increased in the cortex of MCA occluded diabetic rats. Bcl2 expression was not changed in any of the groups. In the hippocampus, DNA fragmentation was not evident in control rats but was observed in diabetic rats. Ischemic injury did not enhance DNA laddering in diabetic animals. The expression of Bax was increased in diabetic rats but was not increased following MCA occlusion. Bcl2 expression was not changed by ischemia in any of the animal models. These data suggest that diabetes may enhance the development of stroke via increased cortical apoptotic activity but this was not additive in the hippocampus following ischemic injury.
authors.affiliation: Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Zhen-guo
authors.initials: ZG
authors.lastname: Li
authors.forename: Mark
authors.initials: M
authors.lastname: Britton
authors.forename: Anders A F
authors.initials: AA
authors.lastname: Sima
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000097:blood; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D053938:DNA Fragmentation; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D008297:Male; D020768:Middle Cerebral Artery / Q000293:injuries / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases