Neurogenesis and Gliogenesis in the Postischemic Brain

Abstract

Stem cells are found throughout the adult mammalian brain, including the subventricular zone (SVZ) adjacent to the lateral ventricles, and in the hippocampal dentate subgranular zone (SGZ). Cells born in the SVZ migrate to the olfactory bulb. Those born in the SGZ migrate into the granule cell layer. Following 5 or 10 min of global ischemia in the adult gerbil, there is a tenfold increase in the birth of new cells in the SGZ as assessed using bromo-deoxy-uridine incorporation. This begins at 7 days, peaks at 11 days, and decreases thereafter. Over the ensuing month, approximately one-fourth of the newborn cells disappear. Of the remaining cells, 60% migrate into the granule cell layer where two-thirds of these become NeuN, calbindin, and MAP-2 immunostained neurons. The remaining 40% of the cells migrate into the dentate hilus where one-fourth of these become glial fibrillary acidic protein-labeled astrocytes. Death of CA1 pyramidal neurons does not stimulate neurogenesis because ischemia-induced tolerance—which does not produce CA1 injury—also stimulated cell proliferation. It is proposed that ischemia-induced neurogenesis contributes to the recovery of function, specifically of anterograde and retrograde recent memory function that is lost following global ischemia in man.