Hypoglycemia Induces Transient Neurogenesis and Subsequent Progenitor Cell Loss in the Rat Hippocampus

Abstract

Neurogenesis after brain injury not only leads to the replacement of damaged cells but might also contribute to functional recovery, suggesting the possibility of endogenous neural repair. We investigated the extent of hippocampal neural regeneration in a rat model of hypoglycemia. Two weeks after 30 min of insulin-induced isoelectric electroencephalogram, extensive neuronal loss was observed in the hippocampus, including area CA1 and dentate gyrus (DG). A transient increase in progenitor cell proliferation in the DG subgranular zone (SGZ) was detected, leading to an increase of immature neuroblasts 1-2 weeks after hypoglycemic insult. Most of the surviving newborn cells assumed a neuronal phenotype within 1 month in DG, a few cells near the site of granule-cell death becoming astroglia or microglia. No neuronal regeneration was observed in the CA1 after hypoglycemia, although dividing cells appeared to be astroglia or microglia in CA1 and dentate hilus. At 4 weeks after hypoglycemia, proliferative activity in the SGZ diminished below baseline in experimental versus control rats, with a subsequent reduction of neuroblasts. Morphological findings (doublecortin staining) suggest permanent progenitor cell loss in some areas of SGZ. Reduced neurogenesis in DG and lack of neuronal regeneration in CA1 may impede cognitive recovery after severe hypoglycemia injury.