title: Aging is neuroprotective during global ischemia but leads to increased caspase-3 and apoptotic activity in hippocampal neurons.
abstract: Previously, we found a significantly greater number of surviving CA1 neurons to global ischemia in the aged (24-month-old) F344 rats than in young (4-month-old) rats. The present study tests the hypothesis that aging retards neuronal death in the hippocampal CA1 region following cerebral ischemia. The CA1 "living cell ratio" was significantly greater in aged than in young rats at three days (62+/-8% vs. 30+/-8%) and at eight days (36+/-6% vs. 17+/-5%), but not at 14 days (15+/-12% vs. 18+/-12%) following ischemia. The number of the CA1 cells exhibiting co-localized TdT-mediated X-dUTP nick end labeling reaction and caspase-3 active peptide (C3AP) immunoreactivity was greater in aged than young animals at three and eight days following ischemia (36+/-8/mm vs. 3+/-1/mm and 36+/-14 vs. 0+/-0, p<0.05 respectively). Also, the total number of C3AP-positive cells in the CA1 region in the aged group was significantly greater than in the young group at three and eight days post-ischemia (p<0.05). Aging appears to delay caspase-3-dependent apoptotic cell death induced by global ischemia in the CA1 region of the hippocampus, consistent with an age-induced neuroprotective process.
authors.affiliation: Department of Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA. he.zhen@mayo.edu
authors.forename: Zhen
authors.initials: Z
authors.lastname: He
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Brott
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Michael
authors.initials: M
authors.lastname: McKinney
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases