Advanced

Patterns of cell death and dopaminergic neuron survival in intrastriatal nigral grafts

Emgård-Mattson, Mia LU ; Karlsson, Jenny LU ; Hansson, Oskar LU and Brundin, Patrik LU (1999) In Experimental Neurology 160(1). p.88-279
Abstract
Previous studies indicate that 80-95% of grafted dopamine neurons die following implantation of embryonic ventral mesencephalic tissue into the striatum. It is believed that the majority die within the first 1-3 weeks after surgery. The aim of this study was to study when and where the implanted neurons die, using the novel fluorescent stain Fluoro-Jade. Fluoro-Jade has recently been shown to stain cell bodies, dendrites, axons, and terminals of degenerating neurons. We transplanted dissociated ventral mesencephalic tissue from embryonic day 14 rat embryos into intact adult rat striatum. After perfusion and sectioning of the implanted rat brains, the number and distribution of Fluoro-Jade and tyrosine hydroxylase-positive neurons were... (More)
Previous studies indicate that 80-95% of grafted dopamine neurons die following implantation of embryonic ventral mesencephalic tissue into the striatum. It is believed that the majority die within the first 1-3 weeks after surgery. The aim of this study was to study when and where the implanted neurons die, using the novel fluorescent stain Fluoro-Jade. Fluoro-Jade has recently been shown to stain cell bodies, dendrites, axons, and terminals of degenerating neurons. We transplanted dissociated ventral mesencephalic tissue from embryonic day 14 rat embryos into intact adult rat striatum. After perfusion and sectioning of the implanted rat brains, the number and distribution of Fluoro-Jade and tyrosine hydroxylase-positive neurons were evaluated at 6, 10, 14, and 42 days posttransplantation. Intensely Fluoro-Jade stained neurons were numerous in the grafts at 6 and 10 days after graft surgery; appeared in reduced numbers at 14 days; and had disappeared by the 42-day time point. The number of surviving tyrosine hydroxylase-positive, dopaminergic neurons in the grafts did not change between 6 and 42 days and the low survival rate confirmed that over 90% of these neurons had died during the first week. Assessment of the distribution of neurons positive for Fluoro-Jade or tyrosine hydroxylase revealed higher numbers of neurons stained for these markers located at the periphery than the center of the grafts, and this pattern did not change over time. This study indicates that transplanted neurons continue to die up to 14 days after grafting. Since the majority of transplanted tyrosine hydroxylase-positive neurons most probably die before 6 days after transplantation, neuroprotective strategies should primarily focus on the transplantation procedure and the first week after implantation. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dopamine, nigral grafts, Fluoro-Jade, cell death, Parkinson's disease, transplantation
in
Experimental Neurology
volume
160
issue
1
pages
88 - 279
publisher
Academic Press
external identifiers
  • pmid:10630212
  • scopus:0345102465
ISSN
0014-4886
DOI
10.1006/exnr.1999.7198
language
English
LU publication?
yes
id
b4c34b13-026f-4e2b-9c26-f31829bbf7fc (old id 1114740)
date added to LUP
2008-07-04 15:57:40
date last changed
2017-09-24 03:28:50
@article{b4c34b13-026f-4e2b-9c26-f31829bbf7fc,
  abstract     = {Previous studies indicate that 80-95% of grafted dopamine neurons die following implantation of embryonic ventral mesencephalic tissue into the striatum. It is believed that the majority die within the first 1-3 weeks after surgery. The aim of this study was to study when and where the implanted neurons die, using the novel fluorescent stain Fluoro-Jade. Fluoro-Jade has recently been shown to stain cell bodies, dendrites, axons, and terminals of degenerating neurons. We transplanted dissociated ventral mesencephalic tissue from embryonic day 14 rat embryos into intact adult rat striatum. After perfusion and sectioning of the implanted rat brains, the number and distribution of Fluoro-Jade and tyrosine hydroxylase-positive neurons were evaluated at 6, 10, 14, and 42 days posttransplantation. Intensely Fluoro-Jade stained neurons were numerous in the grafts at 6 and 10 days after graft surgery; appeared in reduced numbers at 14 days; and had disappeared by the 42-day time point. The number of surviving tyrosine hydroxylase-positive, dopaminergic neurons in the grafts did not change between 6 and 42 days and the low survival rate confirmed that over 90% of these neurons had died during the first week. Assessment of the distribution of neurons positive for Fluoro-Jade or tyrosine hydroxylase revealed higher numbers of neurons stained for these markers located at the periphery than the center of the grafts, and this pattern did not change over time. This study indicates that transplanted neurons continue to die up to 14 days after grafting. Since the majority of transplanted tyrosine hydroxylase-positive neurons most probably die before 6 days after transplantation, neuroprotective strategies should primarily focus on the transplantation procedure and the first week after implantation.},
  author       = {Emgård-Mattson, Mia and Karlsson, Jenny and Hansson, Oskar and Brundin, Patrik},
  issn         = {0014-4886},
  keyword      = {dopamine,nigral grafts,Fluoro-Jade,cell death,Parkinson's disease,transplantation},
  language     = {eng},
  number       = {1},
  pages        = {88--279},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Patterns of cell death and dopaminergic neuron survival in intrastriatal nigral grafts},
  url          = {http://dx.doi.org/10.1006/exnr.1999.7198},
  volume       = {160},
  year         = {1999},
}