Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury

Helen Hellmich, Kristine Eidson, Jeremy Cowart, Jeanna Crookshanks, Deborah K. Boone, Syed Shah, Tatsuo Uchida, Douglas Dewitt, Donald Prough

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Increases of synaptically released zinc and intracellular accumulation of zinc in hippocampal neurons after traumatic or ischemic brain injury is neurotoxic and chelation of zinc has been shown to reduce neurodegeneration. Although our previous studies showed that zinc chelation in traumatically brain-injured rats correlated with an increase in whole-brain expression of several neuroprotective genes and reduced numbers of apoptotic neurons, the effect on functional outcome has not been determined, and the question of whether this treatment may actually be clinically relevant has not been answered. In the present study, we show that treatment of TBI rats with the zinc chelator calcium EDTA reduces the numbers of injured, Fluoro-Jade-positive neurons in the rat hippocampus 24 h after injury but does not improve neurobehavioral outcome (spatial memory deficits) 2 weeks post-injury. Our data suggest that zinc chelation, despite providing short-term histological neuroprotection, fails to improve long-term functional outcome, perhaps because long-term disruptions in homeostatic levels of zinc adversely influence hippocampus-dependent spatial memory.

Original languageEnglish (US)
Pages (from-to)155-159
Number of pages5
JournalNeuroscience Letters
Volume440
Issue number2
DOIs
StatePublished - Aug 1 2008

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Zinc
Neurons
Hippocampus
Memory Disorders
Wounds and Injuries
Brain
Traumatic Brain Injury
Edetic Acid
Brain Injuries
Genes

Keywords

  • Behavioral outcome
  • Traumatic brain injury
  • Zinc chelation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury. / Hellmich, Helen; Eidson, Kristine; Cowart, Jeremy; Crookshanks, Jeanna; Boone, Deborah K.; Shah, Syed; Uchida, Tatsuo; Dewitt, Douglas; Prough, Donald.

In: Neuroscience Letters, Vol. 440, No. 2, 01.08.2008, p. 155-159.

Research output: Contribution to journalArticle

Hellmich, Helen ; Eidson, Kristine ; Cowart, Jeremy ; Crookshanks, Jeanna ; Boone, Deborah K. ; Shah, Syed ; Uchida, Tatsuo ; Dewitt, Douglas ; Prough, Donald. / Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury. In: Neuroscience Letters. 2008 ; Vol. 440, No. 2. pp. 155-159.
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