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Diabetes 55:349-355, 2006
DOI: 10.2337/diabetes.55.02.06.db05-0654
© 2006 by the American Diabetes Association
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Complications

Streptozotocin-Induced Diabetes Causes Astrocyte Death After Ischemia and Reperfusion Injury

Marianna Muranyi1, Chaonan Ding2, QingPing He2, Yanling Lin2, and Ping-An Li1,2,3

1 Department of Complementary and Alternative Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii
2 Laboratory for Experimental Neurology, Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii
3 Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii

Address correspondence and reprint requests to Ping-An Li, Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, 1960 East West Rd., Biomedical Building, Room T514, Honolulu, HI 96822. E-mail: pali{at}pbrc.hawaii.edu

Key Words: 8-OHdG, 8-hydroxy-2-deoxyguanosine • CNS, central nervous system • GFAP, glial fibrillary acidic protein • HEt, hydroethidine • iNOS, inducible NO synthase • ONOO–, peroxynitrite • RNS, reactive nitrogen species • ROS, reactive oxygen species

Diabetes exacerbates neuronal cell death induced by cerebral ischemia. One contributing factor is enhanced acidosis during ischemia. Astrocytes are vulnerable to hypoxia under acidic conditions in vitro and may be targets of ischemia under diabetic conditions. The objective of this study was to determine whether diabetes would cause damage to astrocytes after an ischemic brain injury in vivo. Diabetic and nondiabetic rats were subjected to 5 min of forebrain ischemia and followed by 30 min, 6 h, or 1 or 3 days of recovery. The results showed that ischemia caused activation of astrocytes in nondiabetic rats. In contrast, diabetes caused astrocyte activation in early stage of reperfusion and astrocyte death in late stage of reperfusion. Remarkable astrocyte death was preceded by increased DNA oxidation. Further studies revealed that increased astrocyte damage coincided with enhanced production of free radicals. These data suggest that hyperglycemic ischemia worsens outcome in astrocytes, as it does in neurons.


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Copyright © 2006 by the American Diabetes Association.