Protein aggregation after focal brain ischemia and reperfusion

Bing Ren Hu, Shorena Janelidze, Myron D. Ginsberg, Raul Busto, Miguel Perez-Pinzon, Thomas J. Sick, Bo K. Siesjö, C. L. Liu

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

Two hours of transient focal brain ischemia causes acute neuronal death in the striatal core region and a somewhat more delayed type of neuronal death in neocortex. The objective of the current study was to investigate protein aggregation and neuronal death after focal brain ischemia in rats. Brain ischemia was induced by 2 hours of middle cerebral artery occlusion. Protein aggregation was analyzed by electron microscopy, laser-scanning confocal microscopy, and Western blotting. Two hours of focal brain ischemia induced protein aggregation in ischemic neocortical neurons at 1 hour of reperfusion, and protein aggregation persisted until neuronal death at 24 hours of reperfusion. Protein aggregates were found in the neuronal soma, dendrites, and axons, and they were associated with intracellular membranous structures during the postischemic phase. High-resolution confocal microscopy showed that clumped protein aggregates surrounding nuclei and along dendrites were formed after brain ischemia. On Western blots, ubiquitinated proteins (ubi-proteins) were dramatically increased in neocortical tissues in the postischemic phase. The ubi-proteins were Triton-insoluble, indicating that they might be irreversibly aggregated. The formation of ubi-protein aggregates after ischemia correlated well with the observed decrease in free ubiquitin and neuronal death. The authors concluded that proteins are severely damaged and aggregated in neurons after focal ischemia. The authors propose that protein damage or aggregation may contribute to ischemic neuronal death.

Original languageEnglish (US)
Pages (from-to)865-875
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number7
DOIs
StatePublished - 2001

Keywords

  • Electron microscopy
  • Endoplasmic reticulum
  • Ethanolic phosphotungstic acid
  • Focal brain ischemia
  • Protein aggregation
  • Ubiquitin
  • Unfolded proteins

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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