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 language | English (US) |
|---|---|
| Pages (from-to) | 119-126 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 1127 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 5 2007 |
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Keywords
- Fluoro-Jade
- Gene expression
- Hippocampal injury
- Newport Green
- Traumatic brain injury
- Zinc neurotoxicity
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury. / Hellmich, Helen; Eidson, Kristine A.; Capra, Bridget A.; Garcia, Jeanna M.; Boone, Deborah R.; Hawkins, Bridget; Uchida, Tatsuo; Dewitt, Douglas; Prough, Donald.
In: Brain Research, Vol. 1127, No. 1, 05.01.2007, p. 119-126.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Injured Fluoro-Jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury
AU - Hellmich, Helen
AU - Eidson, Kristine A.
AU - Capra, Bridget A.
AU - Garcia, Jeanna M.
AU - Boone, Deborah R.
AU - Hawkins, Bridget
AU - Uchida, Tatsuo
AU - Dewitt, Douglas
AU - Prough, Donald
PY - 2007/1/5
Y1 - 2007/1/5
N2 - 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.
AB - 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.
KW - Fluoro-Jade
KW - Gene expression
KW - Hippocampal injury
KW - Newport Green
KW - Traumatic brain injury
KW - Zinc neurotoxicity
UR - http://www.scopus.com/inward/record.url?scp=33845203643&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845203643&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2006.09.094
DO - 10.1016/j.brainres.2006.09.094
M3 - Article
VL - 1127
SP - 119
EP - 126
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -