Analysis of brain injury following intrahippocampal administration of β-amyloid in streptozotocin-treated rats

Matthew D. Smyth, J. Patrick Kesslak, Brian J. Cummings, Carl W. Cotman

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21 Scopus citations


It has been suggested that the vulnerability of the aged brain to Alzheimer's disease (AD) pathogenesis depends on a number of risk factors, including abnormal glycolytic metabolism and β-amyloid accumulation. Intrahippocampal injections of β-amyloid and related peptides were administered to chronically hyperglycemic rats to examine β-amyloid toxicity and the interaction with imbalances of glucose metabolism. Chronic hyperglycemia was induced by systemic injection of streptozotocin (STZ) which selectively destroys pancreatic β-islet cells. Ten days after intrahippocampal injection of synthetic β-amyloid peptides (β1-42, β25-35, scrambled β25-35), lesion volume, blood glucose, and plasma corticosterone concentrations, β1-42 immunoreactivity and gliosis were assessed to determine peptide toxicity in the normoglycemic and hyperglycemic conditions. Glucose levels correlated with plasma corticosterone concentrations (r = 0.85) and increased lesion volume size (r = 0.36). Intrahippocampal peptide injections in normoglycemic subjects did not induce significant damage as compared to control injections of vehicle alone. STZ-treated groups demonstrated a trend for increased lesion volume size following injection of either vehicle, β1-42, or β25-35. The combination of the β1-42 peptide and streptozotocin-induced hyperglycemia was toxic and induced significantly larger lesions (p < 0.01) of the dorsal blade of the dentate gyrus as compared to injections of β1-42 into normoglycemic subjects.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalNeurobiology of Aging
Issue number2
StatePublished - 1994


  • Alzheimer's disease
  • Hippocampus
  • Hyperglycemia
  • Streptozotocin
  • β-amyloid


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