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Intrathecal cyclosporin prolongs survival of late-stage ALS mice

Authors
Journal
Brain Research
0006-8993
Publisher
Elsevier
Publication Date
Volume
894
Issue
2
Identifiers
DOI: 10.1016/s0006-8993(01)02012-1
Keywords
  • Amyotrophic Lateral Sclerosis
  • Neurodegeneration
  • Sod1-G93A Transgenic Mice
  • Mitochondrial Permeability Transition
  • Intrathecal Cyclosporin A
  • Neuroprotection
Disciplines
  • Medicine

Abstract

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.

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