Progressive parenchymal deposition of β-amyloid precursor protein in rat brain following global cerebral ischemia

Baowan Lin, Rainald Schmidt-Kastner, Raul Busto, Myron D. Ginsberg

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

In addition to producing acute neuronal necrosis within selectively vulnerable brain regions, our recent studies have shown that global cerebral ischemia may also be followed by protracted degenerative changes occurring over the course of 10 weeks. Chronic brain pathology may be associated with the abnormal deposition of β-amyloid precursor protein (βAPP). In the present study, we used a monoclonal antibody to the N-terminal portion of βAPP to characterize the brains of rats surviving 1-10 weeks following 10 min of global brain ischemia produced by bilateral carotid artery occlusions plus systemic hypotension. After ischemia, increased βAPP immunolabeling emerged in several brain regions. In the hippocampus, granular deposits appeared in the damaged CA 1 area by 2 weeks, and by 4-10 weeks the remnants of necrotic CA1 neurons were also immunolabeled. In striatum and thalamus, regions with necrotic cell death also revealed granular βAPP deposits. The neocortex was devoid of overt ischemic neuronal damage bur revealed prominent βAPP immunoreactivity. Large ovoid deposits of low-density βAPP immunostaining occurred in cortical neurons at 1-2 weeks. At 4-10 weeks, large round or oval deposits immunoreactive for βAPP appeared in several cortical regions. The highest density of deposits was seen in the temporal and piriform cortices. Our results indicate that abnormal βAPP deposition may result from ischemic as well as chronic neurodegenerative processes.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalActa neuropathologica
Volume97
Issue number4
DOIs
StatePublished - Apr 1 1999

Keywords

  • Amyloid
  • Chronic pathology
  • Immunochemistry
  • Neurodegeneration

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

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