Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats

Zhen He, Julia E. Crook, James F. Meschia, Thomas G. Brott, Dennis W. Dickson, Michael McKinney

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


The present study examines the hypothesis that aging defined by the 50% survival age compromises neuroprotection afforded by ischemic preconditioning (IPC). Sixty-four male F344 rats aged 4- and 24-months, respectively, were subjected to IPC, (3-min ischemia) or sham-surgery followed by 10-min (full) ischemia or sham-surgery 2 days later. There were 4 groups at each age: sham-surgery-sham-surgery (SS), preconditioning-sham-surgery (PS), preconditioning-ischemia (PI) and sham-surgery-ischemia (SI) groups. Assessments of histology and immunoreactivities of N-methyl-D-aspartic acid receptor 1 (NMDAr1) and caspase-3 active peptide (C3AP) in the hippocampal CA1 region were performed 8 days after full ischemia. The CA1 "living cell ratio" was greater in the aged SI group than in the young SI group (32±6% vs. 17±5%, p<0.05), whereas the degree of protection against full ischemia afforded by IPC was reduced in the aged compared with the young (53±17% vs. 241±25%, P<0.0001). The basal level of NMDAr1 immunofluorescence was significantly higher in young animals, while the numbers of C3AP-positive cells were greater in all three aged ischemic groups as compared to respective young groups (p<0.01, p=0.055 and p<0.05). A fourth method of assessing cell damage using Fluoro Jade C labeled degenerating neurons that were also intensively eosinophilic. Counts of Fluoro Jade C-positive cells were higher in the young SI group than in the aged SI group (P<0.05), suggesting that mechanisms of ischemic cell death may change with aging. In conclusion, aging alters mechanisms of ischemic cell death in CA1 neurons and ischemic tolerance mechanisms are blunted by aging.

Original languageEnglish (US)
Pages (from-to)365-374
Number of pages10
JournalCurrent Neurovascular Research
Issue number5
StatePublished - Dec 2005


  • Aging
  • Caspase-3
  • Fluoro Jade C
  • Global ischemia
  • Ischemic tolerance
  • N-methyl-D-aspartic acid receptor 1
  • Preconditioning
  • Rat

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats'. Together they form a unique fingerprint.

Cite this