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Comparison between survival of lazaroid-treated embryonic nigral neurons in cell suspensions, cultures and transplants.

Karlsson, Jenny C LU ; Emgård-Mattson, Mia LU and Brundin, Patrik LU (2002) In Brain Research1966-01-01+01:00 955(1-2). p.268-280
Abstract
Death of transplanted dopaminergic neurons is induced both during preparation of donor tissue and after intrastriatal grafting. Oxidative stress is thought to be partly responsible for this cell death. In the present study we compared the effects of three lipid peroxidation inhibitors, the lazaroids Tirilazad mesylate, U-83836E and U-101033, on survival of embryonic mesencephalic neurons in different paradigms. The lazaroids were equally potent in preventing serum deprivation-induced death of cultured dopaminergic neurons. In a second set of experiments, mesencephalic suspensions were pretreated with lazaroids and cell survival was analyzed immediately after dissociation, after 2 or 24 h in culture or after intrastriatal transplantation.... (More)
Death of transplanted dopaminergic neurons is induced both during preparation of donor tissue and after intrastriatal grafting. Oxidative stress is thought to be partly responsible for this cell death. In the present study we compared the effects of three lipid peroxidation inhibitors, the lazaroids Tirilazad mesylate, U-83836E and U-101033, on survival of embryonic mesencephalic neurons in different paradigms. The lazaroids were equally potent in preventing serum deprivation-induced death of cultured dopaminergic neurons. In a second set of experiments, mesencephalic suspensions were pretreated with lazaroids and cell survival was analyzed immediately after dissociation, after 2 or 24 h in culture or after intrastriatal transplantation. Lazaroid pretreatment failed to protect mesencephalic neurons in the in vitro paradigms and U-101033E did not protect grafted dopaminergic neurons in contrast to the neuroprotective effects previously reported for U-83836E and Tirilazad. Pretreatment with the iron chelator deferoxamine mesylate did not protect cultured or grafted dopaminergic neurons, nor did it improve neuronal survival in the serum deprivation model. U-83836E and U-101033E, but not Tirilazad, prevented cell death induced by the pro-oxidant tert-butyl hydroperoxide in suspensions. In a final experiment, we found that systemic treatment of the graft recipient rat with Tirilazad mesylate (before and during the first 3 days after grafting) improved survival of transplanted dopaminergic neurons to 180% of control values. Our results show that systemic treatment with a lipid peroxidation inhibitor for 3 days can promote graft survival, but also highlights the poor correlation between neuroprotective effect of pharmacological compounds in vitro and in grafts. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dopamine, Graft, Parkinson’s disease, Tirilazad mesylate, U-83836E, U-101033E
in
Brain Research1966-01-01+01:00
volume
955
issue
1-2
pages
268 - 280
publisher
Elsevier
external identifiers
  • wos:000179424800033
  • pmid:12419547
  • scopus:0037111277
ISSN
1872-6240
DOI
10.1016/S0006-8993(02)03601-6
language
English
LU publication?
yes
id
da2a79d8-c24f-41f2-9532-9e6ccf2c6f1e (old id 111295)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12419547&dopt=Abstract
date added to LUP
2007-07-16 12:00:32
date last changed
2017-01-01 04:24:21
@article{da2a79d8-c24f-41f2-9532-9e6ccf2c6f1e,
  abstract     = {Death of transplanted dopaminergic neurons is induced both during preparation of donor tissue and after intrastriatal grafting. Oxidative stress is thought to be partly responsible for this cell death. In the present study we compared the effects of three lipid peroxidation inhibitors, the lazaroids Tirilazad mesylate, U-83836E and U-101033, on survival of embryonic mesencephalic neurons in different paradigms. The lazaroids were equally potent in preventing serum deprivation-induced death of cultured dopaminergic neurons. In a second set of experiments, mesencephalic suspensions were pretreated with lazaroids and cell survival was analyzed immediately after dissociation, after 2 or 24 h in culture or after intrastriatal transplantation. Lazaroid pretreatment failed to protect mesencephalic neurons in the in vitro paradigms and U-101033E did not protect grafted dopaminergic neurons in contrast to the neuroprotective effects previously reported for U-83836E and Tirilazad. Pretreatment with the iron chelator deferoxamine mesylate did not protect cultured or grafted dopaminergic neurons, nor did it improve neuronal survival in the serum deprivation model. U-83836E and U-101033E, but not Tirilazad, prevented cell death induced by the pro-oxidant tert-butyl hydroperoxide in suspensions. In a final experiment, we found that systemic treatment of the graft recipient rat with Tirilazad mesylate (before and during the first 3 days after grafting) improved survival of transplanted dopaminergic neurons to 180% of control values. Our results show that systemic treatment with a lipid peroxidation inhibitor for 3 days can promote graft survival, but also highlights the poor correlation between neuroprotective effect of pharmacological compounds in vitro and in grafts.},
  author       = {Karlsson, Jenny C and Emgård-Mattson, Mia and Brundin, Patrik},
  issn         = {1872-6240},
  keyword      = {Dopamine,Graft,Parkinson’s disease,Tirilazad mesylate,U-83836E,U-101033E},
  language     = {eng},
  number       = {1-2},
  pages        = {268--280},
  publisher    = {Elsevier},
  series       = {Brain Research1966-01-01+01:00},
  title        = {Comparison between survival of lazaroid-treated embryonic nigral neurons in cell suspensions, cultures and transplants.},
  url          = {http://dx.doi.org/10.1016/S0006-8993(02)03601-6},
  volume       = {955},
  year         = {2002},
}