Caspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia.
Metab Brain Dis
; 17(3): 143-51, 2002 Sep.
Article
in En
| MEDLINE
| ID: mdl-12322785
ABSTRACT
Cerebral ischemia initiates a program of cell death known as apoptosis. Early steps in these death promoting events are the release of cytochrome c from the mitochondria and activation of caspase-9. The purpose of this report is to determine if the administration of a specific caspase-9 inhibitor, Z-Leu-Glu(Ome)-His-Asp(Ome)-FMK x TFA (Z-LEHD-FMK) would attenuate apoptosis and the resultant brain injury after ischemia. Adult Wistar rats underwent 3 h of temporary middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. An intraventricular injection of 4.8 microg of Z-LEHD-FMK was given 15-min postreperfusion. Administration of the caspase-9 inhibitor, Z-LEHD-FMK, to the experimental group (n = 12) reduced total infarction volume by 49% (p < 0.05) and improved neurological outcome by 63% (p < 0.01) as compared to the control group (n = 12). Western blot analysis of animals that underwent ischemia-reperfusion showed the appearance of the active form of caspase-9. Inhibition of caspase-9, the apical caspase in cytochrome-c-dependent apoptosis, is an effective intervention to attenuate neurological injury after focal ischemia.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Ischemia
/
Enzyme Inhibitors
/
Caspase Inhibitors
Limits:
Animals
Language:
En
Journal:
Metab Brain Dis
Journal subject:
CEREBRO
/
METABOLISMO
Year:
2002
Document type:
Article
Affiliation country: