Neurodegeneration in the thalamus following neonatal hypoxia-ischemia is programmed cell death.
We studied neuronal cell body, axonal, and terminal degeneration in brains from 7-day-old rat pups recovered for 0, 1.5, 3, 6, 24, 48, 72 h, and 6 days following hypoxia-ischemia and identified proteins involved in the delayed neurodegeneration in the thalamus. We found that injury is biphasic with initial necrosis in the ipsilateral forebrain by 3 h following hypoxia-ischemia, in contrast to more delayed and apoptotic-like injury in the ventral-basal thalamus, brainstem, and other remote non-forebrain regions. Prior to the appearance of large numbers of apoptotic profiles in the ventral-basal thalamus, expression of Fas death receptor protein, activated forms of caspase 8 and caspase 3, and pro-apoptotic Bcl-2 proteins are increased. This manuscript combines our data on hypoxic-ischemic injury in the developing brain and presents evidence for at least two forms of neurodegeneration, namely, acute necrosis in the forebrain and delayed neurodegeneration in the thalamus, which is death-receptor-mediated programmed cell death.
Northington
F J
FJ
Eudowood Neonatal Pulmonary Division, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Md, USA. fnorthin@jhmi.edu
Ferriero
D M
DM
Martin
L J
LJ
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000032:analysis; D002540:Cerebral Cortex / Q000166:cytology; D003576:Electron Transport Complex IV / Q000032:analysis; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology*; D009434:Neural Pathways; D009474:Neurons / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D013788:Thalamus / Q000254:growth & development / Q000473:pathology*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000032:analysis
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D003576:Electron Transport Complex IV; D020169:Caspases