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Transplantation of Embryonic Cerebellar Grafts Improves Gait Parameters in Ataxic Lurcher Mice
V. Babuska, Z. Houdek, J. Tuma, Z. Purkartova, J. Tumova, M. Kralickova, F. Vozeh, J. Cendelin,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 2002-03-01 to 1 year ago
Medline Complete (EBSCOhost)
from 2002-01-01 to 1 year ago
Nursing & Allied Health Database (ProQuest)
from 2002-03-01 to 1 year ago
Health & Medicine (ProQuest)
from 2002-03-01 to 1 year ago
Psychology Database (ProQuest)
from 2002-03-01 to 1 year ago
- MeSH
- Time Factors MeSH
- Gait MeSH
- Rotarod Performance Test MeSH
- Cerebellum embryology metabolism transplantation MeSH
- Brain-Derived Neurotrophic Factor metabolism MeSH
- Multiple System Atrophy physiopathology therapy MeSH
- Mice, Neurologic Mutants MeSH
- Mice, Inbred C57BL MeSH
- Mice, Inbred CBA MeSH
- Mice, Transgenic MeSH
- Motor Activity MeSH
- Spinocerebellar Degenerations physiopathology therapy MeSH
- Fetal Tissue Transplantation methods MeSH
- Brain Tissue Transplantation methods MeSH
- Treatment Outcome MeSH
- Green Fluorescent Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Hereditary cerebellar ataxias are severe diseases for which therapy is currently not sufficiently effective. One of the possible therapeutic approaches could be neurotransplantation. Lurcher mutant mice are a natural model of olivocerebellar degeneration representing a tool to investigate its pathogenesis as well as experimental therapies for hereditary cerebellar ataxias. The effect of intracerebellar transplantation of embryonic cerebellar solid tissue or cell suspension on motor performance in adult Lurcher mutant and healthy wild-type mice was studied. Brain-derived neurotrophic factor level was measured in the graft and adult cerebellar tissue. Gait analysis and rotarod, horizontal wire, and wooden beam tests were carried out 2 or 6 months after the transplantation. Higher level of the brain-derived neurotrophic factor was found in the Lurcher cerebellum than in the embryonic and adult wild-type tissue. A mild improvement of gait parameters was found in graft-treated Lurcher mice. The effect was more marked in cell suspension grafts than in solid transplants and after the longer period than after the short one. Lurcher mice treated with cell suspension and examined 6 months later had a longer hind paw stride (4.11 vs. 3.73 mm, P < 0.05) and higher swing speed for both forepaws (52.46 vs. 32.79 cm/s, P < 0.01) and hind paws (63.46 vs. 43.67 cm/s, P < 0.001) than controls. On the other hand, classical motor tests were not capable of detecting clearly the change in the motor performance. No strong long-lasting negative effect of the transplantation was seen in wild-type mice, suggesting that the treatment has no harmful impact on the healthy cerebellum.
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- $a Hereditary cerebellar ataxias are severe diseases for which therapy is currently not sufficiently effective. One of the possible therapeutic approaches could be neurotransplantation. Lurcher mutant mice are a natural model of olivocerebellar degeneration representing a tool to investigate its pathogenesis as well as experimental therapies for hereditary cerebellar ataxias. The effect of intracerebellar transplantation of embryonic cerebellar solid tissue or cell suspension on motor performance in adult Lurcher mutant and healthy wild-type mice was studied. Brain-derived neurotrophic factor level was measured in the graft and adult cerebellar tissue. Gait analysis and rotarod, horizontal wire, and wooden beam tests were carried out 2 or 6 months after the transplantation. Higher level of the brain-derived neurotrophic factor was found in the Lurcher cerebellum than in the embryonic and adult wild-type tissue. A mild improvement of gait parameters was found in graft-treated Lurcher mice. The effect was more marked in cell suspension grafts than in solid transplants and after the longer period than after the short one. Lurcher mice treated with cell suspension and examined 6 months later had a longer hind paw stride (4.11 vs. 3.73 mm, P < 0.05) and higher swing speed for both forepaws (52.46 vs. 32.79 cm/s, P < 0.01) and hind paws (63.46 vs. 43.67 cm/s, P < 0.001) than controls. On the other hand, classical motor tests were not capable of detecting clearly the change in the motor performance. No strong long-lasting negative effect of the transplantation was seen in wild-type mice, suggesting that the treatment has no harmful impact on the healthy cerebellum.
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