Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activation.
Caspase activation occurs within 1h of reperfusion in discrete cell populations of the adult rat brain following transient forebrain ischemia. Based on the proximity of these cells to regions of adult neurogenesis and the known susceptibility of developing neurons to apoptosis, we tested the hypothesis that rapidly triggered post-ischemic caspase activation occurs in immature neurons or neuroprogenitor cells. Adult male Long Evans rats were injected with BrdU to label mitotic cells 1, 7, or 28 days prior to being studied. Rats were then subjected to either sham surgery or 10-min transient forebrain ischemia. At 1h after reperfusion, rats underwent perfusion fixation and brains prepared for immunohistochemical analysis. Immunolabeling for caspase-substrate cleavage, using an antibody directed at the caspase derived fragment of alpha-spectrin, was observed in discrete cell populations of the rostral dentate gyrus, dorsal striatum, extreme paramedian CA1 hippocampus, indusium gresium, olfactory tubercle, and thalamus. No cells double-labeled for caspase-substrate cleavage and BrdU at any time point after BrdU injection. Furthermore, cells immunolabeled for caspase-substrate cleavage did not double-label for markers of immature neurons (doublecortin) or progenitor cells (nestin), but did double-label for the mature neuronal marker NeuN. These results indicate that the phenomenon of rapidly triggered caspase activation in the adult rat brain after transient forebrain ischemia is specific to mature neurons and does not occur in neuroprogenitor cells or immature neurons.
Chen
Zhaoming
Z
Department of Emergency Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.
Kontonotas
Diana
D
Friedmann
Daniel
D
Pitts-Kiefer
Alex
A
Frederick
James R
JR
Siman
Robert
R
Neumar
Robert W
RW
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001973:Bromodeoxyuridine; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002544:Cerebral Infarction / Q000378:metabolism / Q000503:physiopathology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007381:Intermediate Filament Proteins / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013049:Spectrin / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors
D015415:Biomarkers; D004268:DNA-Binding Proteins; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; C492380:NeuN protein, mouse; D009479:Neuropeptides; D009687:Nuclear Proteins; D013049:Spectrin; D020169:Caspases; D001973:Bromodeoxyuridine