The relationship between transient zinc ion fluctuations and redox signaling in the pathways of secondary cellular injury: Relevance to traumatic brain injury

Yuan Li, Bridget Hawkins, Douglas Dewitt, Donald Prough, Wolfgang Maret

Research output: Contribution to journalArticle

21 Scopus citations


A major obstacle that hampers the design of drug therapy for traumatic brain injury is the incomplete understanding of the biochemical pathways that lead to secondary cellular injury and contribute to cell death. One such pathway involves reactive species that generate potentially cytotoxic zinc ion fluctuations as a major executor of neuronal, and possibly glial, cell death. Whether zinc ions released during traumatic brain injury are toxic or protective is controversial but can be approached by investigating the exact concentrations of free zinc ions, the thresholds of compromised zinc buffering capacity, and the mechanism of cellular homeostatic control of zinc. Rapidly stretch-injured rat pheochromocytoma (PC12) cells express cellular zinc ion fluctuations that depend on the production of nitric oxide. Chelation of cellular zinc ions after rapid stretch injury, however, increases cellular reactive oxygen species. In a rat model of traumatic brain injury, parasagittal fluid percussion, analysis of the metal load of metallothionein was used as an indicator of changes in cellular zinc ion concentrations. The combined results from the cellular and in vivo investigations caution against interpreting zinc ion fluctuations in the early phase (24 h) after injury as a primarily cytotoxic event.

Original languageEnglish (US)
Pages (from-to)131-141
Number of pages11
JournalBrain Research
StatePublished - May 12 2010



  • Metallothionein
  • Oxidative stress
  • Pheochromocytoma (pc12) cells
  • Rapid stretch injury
  • Traumatic brain injury
  • Zinc

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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