RGD Reference Report - Activation of cell death pathway after a brief period of global ischemia in diabetic and non-diabetic animals. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Activation of cell death pathway after a brief period of global ischemia in diabetic and non-diabetic animals.

Authors: Ding, C  He, Q  Li, PA 
Citation: Ding C, etal., Exp Neurol. 2004 Aug;188(2):421-9.
RGD ID: 2311321
Pubmed: PMID:15246841   (View Abstract at PubMed)
DOI: DOI:10.1016/j.expneurol.2004.04.013   (Journal Full-text)

Mitochondria play a critical role in the pathogenesis of cerebral ischemia. Acute hyperglycemia has been shown to activate the mitochondria-initiated cell death pathway after an intermediate period of ischemia. The objective of the present study was to determine if diabetic hyperglycemia induced by streptozotocin activates the cell death pathway after a brief period of global ischemia. Five minutes of global ischemia was induced in nondiabetic and diabetic rats. Brain samples were collected after 30 min, 6 h, 1, 3, and 7 days of recirculation as well as from sham-operated controls. Histopathological examination in the hippocampal CA1, CA3, hilus, and dentate gyrus regions, as well as in the cortical and thalamic areas, showed that neuronal death in diabetic animals increased compared to nondiabetic ischemic controls. Neuronal damage maturation occurred after 7 days of recovery in nondiabetic rats, while it was shortened to 3 days of recovery in diabetic animals. Western blot analyses revealed that release of cytochrome c markedly increased after 1 and 3 days of reperfusion in diabetic rats. Caspase-3 activation was evident in the nuclear fraction of the cortex of diabetic rats after 3 days recovery and it was preceded by activation of caspase-9, but not activation of caspase-8. Electron microscopy demonstrated that chromatin condensation and mitochondrial swelling were features of the diabetes-mediated ischemic neuronal damage. However, no apoptotic bodies were observed in any sections examined. These results suggest that a brief period of global ischemia in diabetic animals activates a neuronal cell death pathway involving cytochrome c release, caspase-9 activation, and caspase-3 cleavage, all of which are most likely initiated by early mitochondria damage.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia  ISOCasp9 (Rattus norvegicus)2311321; 2311321associated with Diabetes Mellitus more ...RGD 
transient cerebral ischemia  IEP 2311321associated with Diabetes Mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp9  (caspase 9)

Genes (Mus musculus)
Casp9  (caspase 9)

Genes (Homo sapiens)
CASP9  (caspase 9)


Additional Information