Diabetes activates cell death pathway after transient focal cerebral ischemia.
It is well known that diabetes aggravates brain damage in experimental and clinical stroke subjects. Diabetes accelerates maturation of neuronal damage, increases infarct volume, and induces postischemic seizures. The mechanism by which diabetes increases ischemic brain damage is still elusive. Our previous experiments indicate that mitochondria dysfunction may play a role in neuronal death. The objective of this study is to determine whether streptozotocin-induced diabetes activates cell death pathway after a brief period of focal cerebral ischemia. Both diabetic and nondiabetic rats were subjected to 30 min of transient middle cerebral artery occlusion, followed by 0, 0.5, 3, and 6 h of reperfusion. We first determined the pathological outcomes after 7 days of recovery by histopathology, and then detected key components of programmed cell death pathway using immunocytochemistry coupled with confocal laser-scanning microscopy and Western blot analysis. The results show that the cytosolic cytochrome c increased mildly after reperfusion in nondiabetic samples. This increase was markedly enhanced in diabetic rats in both ischemic focus and penumbra. Subsequently, caspase-3 was activated and poly-ADP ribose polymerase (PARP) was cleaved. Our results suggest that activation of apoptotic cell death pathway may play a pivotal role in exaggerating brain damage in diabetic subjects.
Muranyi
Marianna
M
Pacific Biomedical Research Center and John A. Burns School of Medicine, University of Hawaii, Honolulu 96822, USA.
Fujioka
Masayuki
M
He
QingPing
Q
Han
Angela
A
Yong
Gregory
G
Csiszar
Katalin
K
Li
Ping-An
PA
D000818:Animals; D001921:Brain / Q000473:pathology*; D016923:Cell Death; D003574:Cytochrome c Group / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000473:pathology; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D003574:Cytochrome c Group; D011065:Poly(ADP-ribose) Polymerases