title: Apoptosis and neurogenesis after transient hypoxia in the developing rat brain.
abstract: Perinatal brain damage following a hypoxic-ischemic episode has been considered for a long time as an irreversible phenomenon. However, recent studies have shown that various insults may induce de novo neurogenesis in the adult rodent brain. The present study tested the hypothesis that acute hypoxia may trigger neurogenesis in the developing brain. In vitro, the influence of transient hypoxia was analyzed on the outcome of embryonic rat neurons in culture. In vivo, the temporal profile of brain damage was monitored at the level of the CA1 layer of the hippocampus after the exposure to hypoxia of 1-day-old rats. The extent of cell loss and regeneration was evaluated after staining with DAPI. The characterization of newly generated cells was performed in the subventricular zone at 20 days postexposure by immunohistochemistry. Following hypoxia for 6 hours, neuronal viability in the culture dishes was reduced by 36% at 96 hours, with a significant number of cell nuclei showing apoptosis features. In contrast, a 3-hour hypoxia apparently did not damage cultured neurons whose number increased by 14%. The Bax/Bcl-2 ratio tended to increase after 6-hour hypoxia and to decrease after 3-hour hypoxia. In vivo, hypoxia induced cell damage in the CA1 subfield of the hippocampus, where the total number of cells was reduced by 27% at days 6-7 postreoxygenation, with histopathological hallmarks of apoptosis. This cell deficit was followed by a gradual recovery observable from day 20, suggesting a repair mechanism. Brain incorporation of BrdU in the subventricular zone revealed an accumulation of proliferating cells expressing the neuronal marker NeuroD. The present data demonstrate that a posthypoxic neurogenesis does occur during development and may account for brain protection.
authors.affiliation: Laboratoire de Biochimie, INSERM EMI 0014, Faculté de Médecine de Nancy, France. Jean-Luc.Daval@nancy.inserm.fr
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Daval
authors.forename: Paul
authors.initials: P
authors.lastname: Vert
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001707:Biopsy, Needle; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000473:pathology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012680:Sensitivity and Specificity; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases