Comparison between survival of lazaroid-treated embryonic nigral neurons in cell suspensions, cultures and transplants.
(2002) In Brain Research 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/111295
- author
- Karlsson, Jenny C LU ; Emgård-Mattson, Mia LU and Brundin, Patrik LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Dopamine, Graft, Parkinson’s disease, Tirilazad mesylate, U-83836E, U-101033E
- in
- Brain Research
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine and Gene Therapy (0131000135), Neuronal Survival (013212041), Lung Biology (013212002), Department of Experimental Medical Science (013210000)
- 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
- 2016-04-01 11:38:57
- date last changed
- 2022-01-26 08:11:09
@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}},
keywords = {{Dopamine; Graft; Parkinson’s disease; Tirilazad mesylate; U-83836E; U-101033E}},
language = {{eng}},
number = {{1-2}},
pages = {{268--280}},
publisher = {{Elsevier}},
series = {{Brain Research}},
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}},
doi = {{10.1016/S0006-8993(02)03601-6}},
volume = {{955}},
year = {{2002}},
}