Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury

Helen L. Hellmich, Kristine A. Eidson, Bridget A. Capra, Jeanna M. Garcia, Deborah R. Boone, Bridget E. Hawkins, Tatsuo Uchida, Douglas S. DeWitt, Donald S. Prough

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Hippocampal damage contributes to cognitive dysfunction after traumatic brain injury (TBI). We previously showed that Fluoro-Jade, a fluorescent stain that labels injured, degenerating brain neurons, quantifies the extent of hippocampal injury after experimental fluid percussion TBI in rats. Coincidentally, we observed that injured neurons in the rat hippocampus also stained with Newport Green, a fluorescent dye specific for free ionic zinc. Here, we show that, regardless of injury severity or therapeutic intervention, the post-TBI population of injured neurons in rat hippocampal subfields CA1, CA3 and dentate gyrus is indistinguishable, both in numbers and anatomical distribution, from the population of neurons containing high levels of zinc. Treatment with lamotrigine, which inhibits presynaptic release of glutamate and presumably zinc that is co-localized with glutamate, reduced numbers of Fluoro-Jade-positive and Newport Green-positive neurons equally as did treatment with nicardipine, which blocks voltage-gated calcium channels through which zinc enters neurons. To confirm using molecular techniques that Fluoro-Jade and Newport Green-positive neurons are equivalent populations, we isolated total RNA from 25 Fluoro-Jade-positive and 25 Newport Green-positive pyramidal neurons obtained by laser capture microdissection (LCM) from the CA3 subfield, linearly amplified the mRNA and used quantitative ribonuclease protection analysis to demonstrate similar expression of mRNA for selected TBI-induced genes. Our data suggest that therapeutic interventions aimed at reducing neurotoxic zinc levels after TBI may reduce hippocampal neuronal injury.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalBrain Research
Volume1127
Issue number1
DOIs
StatePublished - Jan 5 2007

Keywords

  • Fluoro-Jade
  • Gene expression
  • Hippocampal injury
  • Newport Green
  • Traumatic brain injury
  • Zinc neurotoxicity

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury'. Together they form a unique fingerprint.

  • Cite this

    Hellmich, H. L., Eidson, K. A., Capra, B. A., Garcia, J. M., Boone, D. R., Hawkins, B. E., Uchida, T., DeWitt, D. S., & Prough, D. S. (2007). Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury. Brain Research, 1127(1), 119-126. https://doi.org/10.1016/j.brainres.2006.09.094