Cerebellar diseases causing substantial cell loss often lead to severe functional deficits and restoration of cerebellar function is difficult. Neurotransplantation therapy could become a hopeful method, but there are still many limitations and unknown aspects. Studies in a variety of cerebellar mutant mice reflecting heterogeneity of human cerebellar degenerations show promising results as well as new problems and questions to be answered. The aim of this work was to compare the development of embryonic cerebellar grafts in adult B6CBA Lurcher and B6.BR pcd mutant mice and strain-matched healthy wild type mice. Performance in the rotarod test, graft survival, structure, and volume was examined 2 months after the transplantation or sham-operation. The grafts survived in most of the mice of all types. In both B6CBA and B6.BR wild type mice and in pcd mice, colonization of the host's cerebellum was a common finding, while in Lurcher mice, the grafts showed a low tendency to infiltrate the host's cerebellar tissue. There were no significant differences in graft volume between mutant and wild type mice. Nevertheless, B6CBA mice had smaller grafts than their B6.BR counterparts. The transplantation did not improve the performance in the rotarod test. The study showed marked differences in graft integration into the host's cerebellum in two types of cerebellar mutants, suggesting disease-specific factors influencing graft fate.
- MeSH
- modely nemocí na zvířatech * MeSH
- mozeček fyziologie transplantace MeSH
- myši - mutanty neurologické MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši MeSH
- nemoci mozečku patologie terapie MeSH
- neurodegenerativní nemoci patologie terapie MeSH
- přežívání štěpu fyziologie MeSH
- transplantace fetální tkáně metody MeSH
- transplantace mozkové tkáně metody MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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.
- MeSH
- časové faktory MeSH
- chůze (způsob) MeSH
- metoda rotující tyčky MeSH
- mozeček embryologie metabolismus transplantace MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- multisystémová atrofie patofyziologie terapie MeSH
- myši - mutanty neurologické MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši transgenní MeSH
- pohybová aktivita MeSH
- spinocerebelární degenerace patofyziologie terapie MeSH
- transplantace fetální tkáně metody MeSH
- transplantace mozkové tkáně metody MeSH
- výsledek terapie MeSH
- zelené fluorescenční proteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
SCA2 transgenic mice are thought to be a useful model of human spinocerebellar ataxia type 2. There is no effective therapy for cerebellar degenerative disorders, therefore neurotransplantation could offer hope. The aim of this work was to assess the survival and morphology of embryonic cerebellar grafts transplanted into the cerebellum of adult SCA2 mice. Four month-old homozygous SCA2 and negative control mice were treated with bilateral intracerebellar injections of an enhanced green fluorescent protein-positive embryonic cerebellar cell suspension. Graft survival and morphology were examined three months later. Graft-derived Purkinje cells and the presence of astrocytes in the graft were detected immunohistochemically. Nissl and hematoxylin-eosin techniques were used to visualize the histological structure of the graft and surrounding host tissue. Grafts survived in all experimental mice; no differences in graft structure, between SCA2 homozygous and negative mice, were found. The grafts contained numerous Purkinje cells but long distance graft-to-host axonal connections to the deep cerebellar nuclei were rarely seen. Relatively few astrocytes were found in the center of the graft. No signs of inflammation or tissue destruction were seen in the area around the grafts. Despite good graft survival and the presence of graft-derived Purkinje cells, the structure of the graft did not seem to promise any significant specific functional effects. We have shown that the graft is available for long-term experiments. Nevertheless, it would be beneficial to search for ways of enhancement of connections between the graft and host.
- MeSH
- mozeček patologie transplantace MeSH
- myši transgenní MeSH
- přežívání štěpu MeSH
- sexuální faktory MeSH
- spinocerebelární ataxie terapie MeSH
- transplantace fetální tkáně * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lurcher mutant mice represent a natural model of olivocerebellar degeneration. They serve as a tool to study pathogenesis, the functional impact of the degeneration as well as therapeutic approaches. Wild type littermates are used as healthy controls. Neurotransplantation may be a promising method of therapy for neurodegenerative diseases. The aim of this work was to compare the long-term survival rate of the solid embryonic cerebellar graft in adult Lurcher mutant and wild type mice of the B6CBA strain and to assess the fundamental structural features of the graft. The graft was obtained from 12-day-old GFP mouse embryos. The brains of host mice were examined histologically 6 months after the transplantation. The graft was identified according to its GFP fluorescence. The graft presence and structure was assessed. The graft survived in all 14 Lurcher mice and in 12 of the 14 wild type mice. Cell migration and fibre sprouting from the graft were poor. No marked differences in the graft morphology between Lurcher mutant and wild type mice were found. The graft survival and appearance were similar to those after a shorter period described in a previous study. This suggests that during the 6 months, no intensive or commonly occurring processes changing the graft had proceeded and that the Lurcher mutant cerebellum niche had no strong influence over the fate of the solid cerebellar graft.
- MeSH
- časové faktory MeSH
- mozeček fyziologie transplantace MeSH
- myši - mutanty neurologické MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši transgenní MeSH
- myši MeSH
- přežívání štěpu * fyziologie MeSH
- transplantace fetální tkáně metody trendy MeSH
- transplantace mozkové tkáně metody trendy MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lurcher mutant mice represent a model of olivocerebellar degeneration. They are used to investigate cerebellar functions, consequences of cerebellar degeneration and methods of therapy influencing them. The aim of the work was to assess the effect of foetal cerebellar graft transplantation, repeated enforced physical activity and the combination of both these types of treatment on motor skills, spontaneous motor activity and spatial learning ability in adult B6CBA Lurcher mice. Foetal cerebellar grafts were applied into the cerebellum of Lurchers in the form of solid tissue pieces. Enforced motor activity was realised through rotarod training. Motor functions were examined using bar, ladder and rotarod tests. Spatial learning was tested in the Morris water maze. Spontaneous motor activity in the open field was observed. The presence of the graft was examined histologically. Enforced physical activity led to moderate improvement of some motor skills and to a significant amelioration of spatial learning ability in Lurchers. The transplantation of cerebellar tissue did not influence motor functions significantly but led to an improvement of spatial learning ability. Mutual advancement of the effects of both types of treatment was not observed. Spontaneous motor activity was influenced neither by physical activity nor by the transplantation. Physical activity did not influence the graft survival and development. Because nerve sprouting and cell migration from the graft to the host cerebellum was poor, the functional effects of the graft should be explained with regard to its trophic influence rather than with any involvement of the grafted cells into neural circuitries.
- MeSH
- degenerace nervu chirurgie MeSH
- financování organizované MeSH
- metoda rotující tyčky MeSH
- mozeček embryologie patologie transplantace MeSH
- myši - mutanty neurologické chirurgie MeSH
- myši MeSH
- nucleus olivaris caudalis patologie MeSH
- pohybová aktivita fyziologie MeSH
- reakční čas MeSH
- těhotenství MeSH
- transplantace fetální tkáně metody patologie MeSH
- učení fyziologie MeSH
- vnímání prostoru fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
svazky ; 28 cm
- MeSH
- hojení ran MeSH
- kraniofaciální abnormality chirurgie MeSH
- limbický systém transplantace MeSH
- mikrochirurgie MeSH
- plastická chirurgie MeSH
- tkáňové inženýrství MeSH
- transplantace fetální tkáně MeSH
- zákroky plastické chirurgie MeSH
- Publikační typ
- abstrakty MeSH
- kongresy MeSH
- sborníky MeSH
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- plastická chirurgie
1. Neural transplantation in Huntington's diseased patients is currently the only approach in the treatment of this neurodegenerative disorder. The clinical trial, unfortunately, includes only a small number of patients until now, since many important questions have not been answered yet. One of them is only mild to moderate improvement of the state in most of grafted patients. 2. We examined the morphological correlates in the response to intrastriatal grafting of fragments of foetal rat ventral mesencephalic tissue 1 month after transplantation in male Wistar rats within varying durations (from 2 to 38 weeks) of experimentally induced neurodegenerative process of the striatum (used as a model of Huntington's disease). Our goal was to determine the impact of advanced striatal damage and gliosis on the graft viability and host-graft integration. 3. The findings can be summarized as follows: The progressive reactive gliosis, which is not able to compensate continual reduction of the grey matter leading to an extensive atrophy of the striatum in a long-term lesions, results in formation of the compact glial network. This tissue cannot be considered the suitable terrain for successful graft development and formation of host-graft interconnections. 4. The progression of irreversible morphological changes in long-lasting neurodegenerative process within the striatum can be supposed one of the important factors, which may decrease our prospect of distinct improvement after neural grafting in patients in advanced stage of Huntington's disease, who still remain the leading group in clinical trials.
- MeSH
- bazální ganglia embryologie patologie transplantace MeSH
- glióza patologie MeSH
- Huntingtonova nemoc patologie terapie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- progrese nemoci MeSH
- transplantace fetální tkáně MeSH
- transplantace mozkové tkáně patologie MeSH
- transplantace MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- fetální krev MeSH
- kmenové buňky MeSH
- lidé MeSH
- odběr fetální krve metody využití MeSH
- těhotenství MeSH
- transplantace fetální tkáně metody využití MeSH
- transplantace kmenových buněk MeSH
- transplantace kostní dřeně metody využití MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- Publikační typ
- přehledy MeSH
