Effects of postnatal hyperoxia exposure on the rat dentate gyrus and subventricular zone

Premature newborns may be exposed to hyperoxia in the first postnatal period, but clinical and experimental works have raised the question of oxygen toxicity for the developing brain. However, specific analysis of hyperoxia exposure on neurogenesis is still lacking. Thus, the aim of the present study was to evaluate possible changes in the morphometric parameters of the main neurogenic sites in newborn rats exposed to 60 or 95 % oxygen for the first 14 postnatal days. The optical disector, a morphometric method based upon unbiased sampling principles of stereology, was applied to analyse cell densities, total volumes, and total cell numbers of the dentate gyrus (DG) and subventricular zone (SVZ). Apoptosis and proliferation were also studied by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling method and anti-ki67 immunohistochemistry, respectively. Severe hyperoxia increased the percentage of apoptotic cells in the DG. Moderate and severe hyperoxia induced a proliferative response both in the DG and SVZ, but the two neurogenic sites showed different changes in their morphometric parameters. The DG of both the hyperoxic groups showed lower volume and total cell number than that of the normoxic one. Conversely, the SVZ of newborn rats exposed to 95 % hyperoxia showed statistically significant higher volume and total cell number than SVZ of rats raised in normoxia. Our findings indicate that hyperoxia exposure in the first postnatal period affects both the neurogenic areas, although in different ways, i.e. reduction of DG and expansion of SVZ.