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Intrathecal cyclosporin prolongs survival of late-stage ALS mice

Keep, Marcus; Elmer, Eskil LU ; Fong, Keith S. and Csiszar, Katalin (2001) In Brain Research1966-01-01+01:00 894(2). p.327-331
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by upper and lower motor neuron death with ascending paralysis leading to death. In a transgenic mouse model of ALS (SOD1-G93A) weakness appears at 3 months of age, and because of progressive paralysis leads to death by 5 months. Cyclosporin A (CsA) is well known, for its extracerebral effect, as an immunosuppressant in organ transplantation. When able to access the brain, CsA is an effective neuroprotective agent mainly due to its protection of mitochondria through inhibition of the mitochondrial permeability transition. CsA does not cross the intact blood-brain barrier and was in the present study delivered to the brain through an infusion into the lateral... (More)
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by upper and lower motor neuron death with ascending paralysis leading to death. In a transgenic mouse model of ALS (SOD1-G93A) weakness appears at 3 months of age, and because of progressive paralysis leads to death by 5 months. Cyclosporin A (CsA) is well known, for its extracerebral effect, as an immunosuppressant in organ transplantation. When able to access the brain, CsA is an effective neuroprotective agent mainly due to its protection of mitochondria through inhibition of the mitochondrial permeability transition. CsA does not cross the intact blood-brain barrier and was in the present study delivered to the brain through an infusion into the lateral cerebral ventricle. Injections started at the onset of late disease when weakness of the hindlimbs was apparent. CsA treatment prolonged the survival of ALS transgenic mice as compared to vehicle-treated controls. This finding implicates mitochondrial function in ALS and may have significance for human disease. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Amyotrophic lateral sclerosis, Neurodegeneration, SOD1-G93A transgenic mice, Mitochondrial permeability transition, Intrathecal cyclosporin A, Neuroprotection
in
Brain Research1966-01-01+01:00
volume
894
issue
2
pages
327 - 331
publisher
Elsevier
external identifiers
  • pmid:11251210
  • scopus:0035896440
ISSN
1872-6240
DOI
10.1016/S0006-8993(01)02012-1
language
English
LU publication?
yes
id
1734c5e9-4b9b-4593-a197-02779ae485f8 (old id 1120666)
date added to LUP
2008-07-01 13:14:12
date last changed
2018-01-07 06:13:35
@article{1734c5e9-4b9b-4593-a197-02779ae485f8,
  abstract     = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by upper and lower motor neuron death with ascending paralysis leading to death. In a transgenic mouse model of ALS (SOD1-G93A) weakness appears at 3 months of age, and because of progressive paralysis leads to death by 5 months. Cyclosporin A (CsA) is well known, for its extracerebral effect, as an immunosuppressant in organ transplantation. When able to access the brain, CsA is an effective neuroprotective agent mainly due to its protection of mitochondria through inhibition of the mitochondrial permeability transition. CsA does not cross the intact blood-brain barrier and was in the present study delivered to the brain through an infusion into the lateral cerebral ventricle. Injections started at the onset of late disease when weakness of the hindlimbs was apparent. CsA treatment prolonged the survival of ALS transgenic mice as compared to vehicle-treated controls. This finding implicates mitochondrial function in ALS and may have significance for human disease.},
  author       = {Keep, Marcus and Elmer, Eskil and Fong, Keith S. and Csiszar, Katalin},
  issn         = {1872-6240},
  keyword      = {Amyotrophic lateral sclerosis,Neurodegeneration,SOD1-G93A transgenic mice,Mitochondrial permeability transition,Intrathecal cyclosporin A,Neuroprotection},
  language     = {eng},
  number       = {2},
  pages        = {327--331},
  publisher    = {Elsevier},
  series       = {Brain Research1966-01-01+01:00},
  title        = {Intrathecal cyclosporin prolongs survival of late-stage ALS mice},
  url          = {http://dx.doi.org/10.1016/S0006-8993(01)02012-1},
  volume       = {894},
  year         = {2001},
}