The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia.
Unilateral hypoxia-ischemia (HI) was induced in C57/BL6 male mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brains, respectively. HI duration was adjusted to obtain a similar extent of brain injury at all ages. Apoptotic mechanisms (nuclear translocation of apoptosis-inducing factor, cytochrome c release and caspase-3 activation) were several-fold more pronounced in immature than in juvenile and adult brains. Necrosis-related calpain activation was similar at all ages. The CA1 subfield shifted from apoptosis-related neuronal death at P5 and P9 to necrosis-related calpain activation at P21 and P60. Oxidative stress (nitrotyrosine formation) was also similar at all ages. Autophagy, as judged by the autophagosome-related marker LC-3 II, was more pronounced in adult brains. To our knowledge, this is the first report demonstrating developmental regulation of AIF-mediated cell death as well as involvement of autophagy in a model of brain injury.
Zhu
C
C
Department of Physiology, Göteborg University, Göteborg, Sweden. changlian.zhu@fysiologi.gu.se
Wang
X
X
Xu
F
F
Bahr
B A
BA
Shibata
M
M
Uchiyama
Y
Y
Hagberg
H
H
Blomgren
K
K
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D001343:Autophagy / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005420:Flavoproteins / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C494830:AIFM1 protein, mouse; C002744:3-nitrotyrosine; D014443:Tyrosine; D045304:Cytochromes c; C505407:CASP3 protein, human; D002154:Calpain; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases