Age-dependent impairment of hippocampal neurogenesis in chronic cerebral hypoperfusion.

Abstract

Acute ischaemic brain damages, including both strokes and local ischaemia, are powerful stimulators of neurogenesis in the dentate gyrus of the hippocampus in adult rats and mice. As no data are available in chronic cerebral hypoperfusion, we investigated neurogenesis in rats after bilateral chronic occlusion of the carotid arteries (2VO). 2VO was performed in 3- and 12-month-old rats. Proliferation was investigated by bromodeoxyuridine uptake and MCM2 nuclear immunoreactivity, neurogenesis by counting doublecortin-IR cells in the subgranular area of the dentate gyrus of the hippocampus. We found increased proliferation and neurogenesis in the subgranular area of the dentate gyrus of the hippocampus in adult (3-month-old) rats 8 days after 2VO. This capability is lost in middle-aged (12-month-old) rats. Our data suggest that 2VO ligation can be a useful model for studying neurogenesis in experimental conditions mimicking long-lasting human pathologies, and also in the exploration of the uncertain relation between chronic brain hypoperfusion and age-related changes of cognitive function.