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Flunarizine improves the survival of grafted dopaminergic neurons

Schierle, Gabriele LU ; Hansson, Oskar LU and Brundin, Patrik LU (1999) In Neuroscience 94(1). p.17-20
Abstract
Embryonic nigral grafts can survive, reinnervate the striatum and reverse functional deficits in both experimental and clinical Parkinsonism. A major drawback is that only around 10% of the implanted dopaminergic neurons survive. The underlying mechanisms leading to this 90% cell death are not fully understood, but oxidative stress and a substantial loss of neurotrophic support are likely to be involved. Hypoxia and mechanical trauma, which are unavoidable during tissue preparation, may be a trigger for cell death. Recent studies have provided evidence that the type of cell death occurring is, to a large extent, apoptotic. Flunarizine is an antagonist of L-, T- and N-type calcium channels, which permits calcium entry into cells via a... (More)
Embryonic nigral grafts can survive, reinnervate the striatum and reverse functional deficits in both experimental and clinical Parkinsonism. A major drawback is that only around 10% of the implanted dopaminergic neurons survive. The underlying mechanisms leading to this 90% cell death are not fully understood, but oxidative stress and a substantial loss of neurotrophic support are likely to be involved. Hypoxia and mechanical trauma, which are unavoidable during tissue preparation, may be a trigger for cell death. Recent studies have provided evidence that the type of cell death occurring is, to a large extent, apoptotic. Flunarizine is an antagonist of L-, T- and N-type calcium channels, which permits calcium entry into cells via a voltage-dependent mechanism. Flunarizine has been shown to protect neurons against death induced by serum deprivation, nerve growth factor deprivation, oxidative stress, axotomy and ischemia. This study was designed to investigate whether flunarizine can protect grafted embryonic dopaminergic neurons from death when implanted in a rat model of Parkinson's disease. Addition of 1 microM flunarizine inhibited cell death in a suspension of cells derived from the rat's ventral mesencephalon and when such a treated suspension was injected into the neostriatum there was a 2.6-fold greater number of surviving dopaminergic neurons, a doubling of the graft volume and a doubling of the volume of the host neostriatum innervated by dopaminergic fibers from the graft, compared with suspensions not exposed to flunarizine. Furthermore, rats injected with cells that had been exposed to flunarizine displayed a greater recovery of function in the amphetamine-induced rotation test. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Parkinson’s disease, voltage-dependent calcium channels, apoptosis, calcium, oxidative stress, rats
in
Neuroscience
volume
94
issue
1
pages
17 - 20
publisher
Elsevier
external identifiers
  • pmid:10613492
  • scopus:0013670016
ISSN
1873-7544
DOI
10.1016/S0306-4522(99)00324-3
language
English
LU publication?
yes
id
d55aeaf0-87a0-461d-a81a-739e158e7eb0 (old id 1114751)
date added to LUP
2008-07-04 16:04:42
date last changed
2017-02-26 03:41:04
@article{d55aeaf0-87a0-461d-a81a-739e158e7eb0,
  abstract     = {Embryonic nigral grafts can survive, reinnervate the striatum and reverse functional deficits in both experimental and clinical Parkinsonism. A major drawback is that only around 10% of the implanted dopaminergic neurons survive. The underlying mechanisms leading to this 90% cell death are not fully understood, but oxidative stress and a substantial loss of neurotrophic support are likely to be involved. Hypoxia and mechanical trauma, which are unavoidable during tissue preparation, may be a trigger for cell death. Recent studies have provided evidence that the type of cell death occurring is, to a large extent, apoptotic. Flunarizine is an antagonist of L-, T- and N-type calcium channels, which permits calcium entry into cells via a voltage-dependent mechanism. Flunarizine has been shown to protect neurons against death induced by serum deprivation, nerve growth factor deprivation, oxidative stress, axotomy and ischemia. This study was designed to investigate whether flunarizine can protect grafted embryonic dopaminergic neurons from death when implanted in a rat model of Parkinson's disease. Addition of 1 microM flunarizine inhibited cell death in a suspension of cells derived from the rat's ventral mesencephalon and when such a treated suspension was injected into the neostriatum there was a 2.6-fold greater number of surviving dopaminergic neurons, a doubling of the graft volume and a doubling of the volume of the host neostriatum innervated by dopaminergic fibers from the graft, compared with suspensions not exposed to flunarizine. Furthermore, rats injected with cells that had been exposed to flunarizine displayed a greater recovery of function in the amphetamine-induced rotation test.},
  author       = {Schierle, Gabriele and Hansson, Oskar and Brundin, Patrik},
  issn         = {1873-7544},
  keyword      = {Parkinson’s disease,voltage-dependent calcium channels,apoptosis,calcium,oxidative stress,rats},
  language     = {eng},
  number       = {1},
  pages        = {17--20},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Flunarizine improves the survival of grafted dopaminergic neurons},
  url          = {http://dx.doi.org/10.1016/S0306-4522(99)00324-3},
  volume       = {94},
  year         = {1999},
}