Neonatal hypoxic–ischemic injury increases forebrain subventricular zone neurogenesis in the mouse

Abstract

Neurogenesis persists throughout life in the rodent subventricular zone (SVZ)–olfactory bulb pathway and increases in the adult after brain insults. The influence of neonatal injury on SVZ neural precursors is unknown. We examined the effects of hypoxia–ischemia (HI) on neonatal mouse SVZ cell proliferation and neurogenesis. Postnatal day 10 (P10) mice underwent right carotid artery ligation followed by 10% O2 exposure for 45 min. The SVZ area and hemispheric injury were quantified morphometrically 1–3 weeks later. Bromodeoxyuridine (BrdU) was used to label proliferating cells, and cell phenotypes of the progeny were identified by immunohistochemistry. HI significantly enlarged the ipsilateral SVZ at P18, P24, and P31, and increases in the SVZ area correlated directly with the degree of hemispheric damage. HI also stimulated cell proliferation and neurogenesis in the SVZ and peri-infarct striatum. Some newborn cells expressed a neuronal phenotype at P24, but not at P31, indicating that neurogenesis was short-lived. These results suggest that augmenting SVZ neuroblast recruitment and survival may improve neural repair after neonatal brain injury.

Keywords

• Doublecortin
• Bromodeoxyuridine
• Neuroblasts
• Neurogenesis
• Subventricular zone
• Hypoxia–ischemia