Involvement of caspase-3 in cell death after hypoxia-ischemia declines during brain maturation.
The involvement of caspase-3 in cell death after hypoxia-ischemia (HI) was studied during brain maturation. Unilateral HI was produced in rats at postnatal day 7 (P7), 15 (P15), 26 (P26), and 60 (P60) by a combination of left carotid artery ligation and systemic hypoxia (8% O2). Activation of caspase-3 and cell death was examined in situ by high-resolution confocal microscopy with anti-active caspase-3 antibody and propidium iodide and by biochemical analysis. The active caspase-3 positive neurons were composed of more than 90% HI damaged striatal and neocortical neurons in P7 pups, but that number was reduced to approximately 65% in striatum and 34% in the neocortex of P15 pups, and approximately 26% in striatum and 2% in neocortex of P26 rats. In P60 rats, less than 4% of the damaged neurons in striatum and less than 1% in neocortex were positive for active caspase-3. Western blot analysis demonstrated that the level of inactive caspase-3 in normal forebrain tissue gradually declined from a high level in young pups to very low levels in adult rats. Concomitantly, HI-induced active caspase-3 was reduced from a relatively high level in P7, to moderate levels in P15 and P26, to a barely detectable level in P60 rats. The authors conclude that the involvement of caspase-3 in the pathogenesis of cell death after HI declines during neuronal maturation. The authors hypothesize that caspase-3 may play a major role in cell death in immature neurons but a minor role in cell death in mature neurons after brain injury.
Hu
B R
BR
Laboratory of Neurochemistry, Queen's Medical Center, Honolulu, Hawaii 96813, USA.
Liu
C L
CL
Ouyang
Y
Y
Blomgren
K
K
Siesjö
B K
BK
D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D051381:Rats; D017208:Rats, Wistar
C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases