Temporally specific proliferation events are induced in the hippocampus following acute focal injury.
In models of global brain injury, such as stroke or epilepsy, a large increase in neurogenesis occurs in the dentate gyrus (DG) days after the damage is induced. In contrast, more focal damage in the DG produces an increase in neurogenesis within 24 hr. To determine how cell proliferation and differentiation differs in the DG after acute injury in the DG, focal electrolytic lesions were made and mitotic activity was assessed at early (1 day) and late (5 day) time points. At the early time point, bromodeoxyuridine (BrdU)-positive cells were diffusely spread throughout the extent of the hippocampus that was ipsilateral to the lesion. No significant increase in the subgranular zone (SGZ) of the DG was observed. When BrdU was administered at the later time point, the number of BrdU+ cells in the SGZ of the DG was significantly increased. This fourfold increase in BrdU+ cells also resulted in a significant increase in neurogenesis, as measured 6 weeks following BrdU administration. This increase in neurogenesis was not observed when BrdU was administered at the early time point. These results indicate that focal injury in the DG activates two temporally specific proliferation events and that enhanced neurogenesis is observed only following a latent period after the lesion is made.
Ernst
Carl
C
The Neuroscience Program, University of British Columbia, Vancouver, British Columbia, Canada.
Christie
Brian R
BR
D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D001973:Bromodeoxyuridine; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D018891:Dentate Gyrus / Q000473:pathology*; D004195:Disease Models, Animal; D053331:Ectodysplasins; D004572:Electrolysis / Q000009:adverse effects; D005452:Fluoresceins; D007839:Functional Laterality / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009930:Organic Chemicals / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000378:metabolism
D053331:Ectodysplasins; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D009930:Organic Chemicals; D048069:Tumor Necrosis Factors; C435731:fluoro jade; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine