Activation of caspase-3 in permanent and transient brain ischaemia in man.
Animal studies have shown brain ischaemia to cause oxidative damage to DNA and activation of caspase-3, leading to apoptosis. These changes may be exacerbated by reperfusion. To assess caspase-3 activation after transient and permanent brain ischaemia in man, we examined brain tissue from patients who had experienced a cardiac arrest with resuscitation or an atherothrombotic brain infarct, and died 12 h to 9 days later. Sections were immunostained for activated caspase-3 or the 89 kDa caspase-3-mediated cleavage product of poly(ADP-ribose) polymerase. Brain ischaemia caused activation of caspase-3 in macrophages/microglia. Some neurons showed delayed activation of caspase-3 after cardiac arrest, but very few in atherothrombotic infarcts. In man, activation of caspase-3 plays little part in neuronal death in atherothrombotic infarcts but may contribute to delayed death of neurons after cardiac arrest.
Love
S
S
Department of Neuropathology, Frenchay Hospital, Bristol, UK.
Barber
R
R
Srinivasan
A
A
Wilcock
G K
GK
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D005260:Female; D006323:Heart Arrest / Q000150:complications; D006801:Humans; D020767:Intracranial Thrombosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012151:Resuscitation / Q000009:adverse effects
D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases