title: Cortical neurogenesis enhanced by chronic perinatal hypoxia.
abstract: Most regions of the mature mammalian brain, including the cerebral cortex, appear to be unable to support the genesis of new neurons. Here, we report that a low level of neurogenesis occurs in the cerebral cortex of the infant mouse brain and is enhanced by chronic perinatal hypoxia. When mice were reared in a low-oxygen environment from postnatal days 3 to 11, approximately 30% of the cortical neurons were lost after the insult; yet this damage was transient. The loss of cortical neuron number, cortical volume, and brain weight were all reversed during the recovery period. At P18, 7 days after the cessation of hypoxia, there was a marked increase in astroglial cell proliferation within the SVZ, as assessed by 5-bromodeoxyuridine (BrdU) incorporation in S-phase cells. One month after BrdU incorporation, 40% more BrdU-positive cells were found in the cerebral cortex of hypoxic-reared as compared to normoxic control mice. Among these newly generated cortical cells, approximately 45% were oligodendrocytes, 35% were astrocytes, and 10% were neurons in both hypoxic and normoxic mice. However, twice as many BrdU-labeled cells expressed neuronal markers in the neocortex in mice recovering from hypoxia as compared to controls. In both hypoxic-reared and normoxic infant/juvenile mice, putative neuroblasts could be seen detaching from the forebrain subventricular zone, migrating through the subcortical white matter and entering the lower cortical layers, 5 to 11 days after their last mitotic division. We suggest that cortical neurogenesis may play a significant role in repairing neuronal losses after neonatal injury.
authors.affiliation: Child Study Center, Yale University Medical School, 230 South Frontage Road, New Haven, CT 06520, USA.
authors.forename: Devon M
authors.initials: DM
authors.lastname: Fagel
authors.forename: Yosif
authors.initials: Y
authors.lastname: Ganat
authors.forename: John
authors.initials: J
authors.lastname: Silbereis
authors.forename: Timothy
authors.initials: T
authors.lastname: Ebbitt
authors.forename: William
authors.initials: W
authors.lastname: Stewart
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
authors.forename: Laura R
authors.initials: LR
authors.lastname: Ment
authors.forename: Flora M
authors.initials: FM
authors.lastname: Vaccarino
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology*; D002552:Cerebral Ventricles / Q000502:physiology; D051959:ELAV Proteins / Q000378:metabolism; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051959:ELAV Proteins; D007211:Indoles; C007293:DAPI; D005680:gamma-Aminobutyric Acid; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine