ABSTRACT
Abstract-Hypoxia is the primary event of neonatal asphyxia, which remains a major cause of brain injury and subsequent neurological disabilities. The effects of a hypoxic episode of varying duration were investigated in vitro by using primary neuronal cell cultures and in vivo in newborn rat pups. Severe hypoxia was shown to induce an age-dependent delayed neuronal death that mainly reflects apoptosis. Before brain cells displayed morphological hallmarks of apoptotic death, hypoxia was shown to promote re-entry into the cell cycle followed by the activation of pro-apoptotic proteins, such as Bax and caspases. By contrast, mild hypoxia was able to trigger neuronal proliferation by stimulating the expression of neurogenic and survival-associated proteins, including proliferating cell nuclear antigen (PCNA) and Bcl-2. Moreover, in vivo studies revealed that hypoxia-induced neuronal apoptosis observed in the vulnerable CA1 subfield of the hippocampus was then followed by an apparent anatomical recovery, which suggests that neurogenesis might occur as a self-repair mechanism in the developing brain.
