Hyperglycemic but not normoglycemic global ischemia induces marked early intraneuronal expression of β-amyloid precursor protein

Baowan Lin, Myron Ginsberg, Raul Busto

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Preischemic hyperglycemia is known to accentuate acute ischemic injury to neurons, microglia, and endothelia. In the present study, we used a monoclonal antibody to the N-terminal portion of β-APP to examine how the immunoreactivity of this normal membrane glycoprotein is differentially influenced by transient cerebral ischemia when carried out under normoglycemic vs. hyperglycemic conditions. Anesthetized, physiologically regulated rats received 12.5 min of global forebrain ischemia by bilateral carotid artery occlusions plus systemic hypotension. Hyperglycemia was induced by intraperitoneal dextrose administration prior to ischemia. One or three days later, brains were examined by β-APP immunohistochemistry. Ischemia under hyperglycemic conditions led to the robust, widespread intraneuronal expression of β-APP immunoreactivity in neocortex, hippocampus, thalamus, and striatum of all 11 rats; this was most prominent at 24 h postischemia. Compared to rats with normoglycemic ischemia, numbers of β-APP-immunopositive neurons in the parietal cortex of hyperglycemic rats were increased by 5.9 fold at 24 h, and by 10.6 fold at 3 days postischemia. β-APP-immunopositive neurons in hyperglycemic rats often exhibited striking morphological alterations typical of ischemic necrosis; however, no β-APP immunoreaction was observed in zones of frank infarction. Brains of normoglycemic rats (n=11), by contrast, showed only weak β-APP immunostaining in occasional non-necrotic pyramidal neurons of parietal neocortex; no necrosis was present in thalamus. In sham-operated hyperglycemic rats, β-APP immunostaining of thalamic neurons was somewhat increased at 24 h. Western analysis revealed that the hyperglycemia-induced intraneuronal overexpression of β-APP was not associated with an overall increase in tissue levels. The results of this study demonstrate that transient forebrain ischemia under hyperglycemic conditions leads to the early intraneuronal expression of β-APP within neuronal populations showing a heightened susceptibility to hyperglycemia-induced accentuation of ischemic injury. Our data suggest that β-APP or its metabolites may be involved in the injury process.

Original languageEnglish
Pages (from-to)107-116
Number of pages10
JournalBrain Research
Volume888
Issue number1
DOIs
StatePublished - Jan 5 2001

Fingerprint

Amyloid beta-Protein Precursor
Ischemia
Hyperglycemia
Neurons
Neocortex
Prosencephalon
Thalamus
Wounds and Injuries
Necrosis
Parietal Lobe
Pyramidal Cells
Transient Ischemic Attack
Membrane Glycoproteins
Brain
Microglia
Carotid Arteries
Hypotension
Infarction
Endothelium
Hippocampus

Keywords

  • Amyloid
  • Hyperglycemia
  • Immunochemistry
  • Rat
  • Selective vulnerability

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hyperglycemic but not normoglycemic global ischemia induces marked early intraneuronal expression of β-amyloid precursor protein. / Lin, Baowan; Ginsberg, Myron; Busto, Raul.

In: Brain Research, Vol. 888, No. 1, 05.01.2001, p. 107-116.

Research output: Contribution to journalArticle

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