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

For many degenerative cerebellar diseases, currently, no effective treatment that would substantially restore cerebellar functions is available. Neurotransplantation could be a promising therapy for such cases. Nevertheless, there are still severe limitations for routine clinical use. The aim of the work was to assess volume and morphology and functional impact on motor skills of an embryonic cerebellar graft injected in the form of cell suspension in Lurcher mutant and wild-type mice of the B6CBA and C3H strains after a 6-month survival period. The grafts survived in the majority of the mice. In both B6CBA and C3H Lurcher mice, most of the grafts were strictly delimited with no tendency to invade the host cerebellum, while in wild-type mice, graft-derived Purkinje cells colonized the host's cerebellum. In C3H Lurcher mice, but not in B6CBA Lurchers, the grafts had smaller volume than in their wild-type counterparts. C3H wild-type mice had significantly larger grafts than B6CBA wild-type mice. No positive effect of the transplantation on performance in the rotarod test was observed. The findings suggest that the niche of the Lurcher mutant cerebellum has a negative impact on integration of grafted cells. This factor seems to be limiting for specific functional effects of the transplantation therapy in this mouse model of cerebellar degeneration.

• MeSH
• druhová specificita MeSH
• longitudinální studie MeSH
• metoda rotující tyčky MeSH
• modely nemocí na zvířatech MeSH
• motorické dovednosti MeSH
• mozeček embryologie   patologie   transplantace   MeSH
• myši - mutanty neurologické MeSH
• myši inbrední C3H MeSH
• myši inbrední CBA MeSH
• myši transgenní MeSH
• nemoci mozečku patologie   patofyziologie   terapie   MeSH
• neurodegenerativní nemoci patologie   patofyziologie   terapie   MeSH
• přežívání štěpu * fyziologie   MeSH
• transplantace mozkové tkáně * MeSH
• zelené fluorescenční proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Neurotransplantation may be a promising approach for therapy of cerebellar diseases characterized by a substantial loss of neurons. Neurotransplantation could rescue neurons from degeneration and maintain cerebellar reserve, facilitate cerebellar compensation, or help reconstruct damaged neural circuits by cell substitution. These mechanisms of action can be of varying importance according to the type of cerebellar disease. Neurotransplantation therapy in cerebellar ataxias is still at the stage of experimental studies. There is currently little knowledge regarding cerebellar patients. Nevertheless, data provided by experiments in animal models of cerebellar degeneration and both clinical studies and experiences in patients with other neurologic diseases enable us to suggest basic principles, expectations, limitations, and future directions of neurotransplantation therapy for cerebellar diseases.

• MeSH
• cerebelární ataxie chirurgie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• transplantace mozkové tkáně metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy 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

Užití mezenchymálních kmenových buněk (MSC) je jedním z experimentálních terapeutických přístupů k léčbě poranění míchy. MSC lze získat z kostní dřeně, tukové tkáně i z jiných periferních tkání dospělých jedinců. Výhodou je, v porovnání s jinými kmenovými buňkami, jejich dobrá dostupnost, snadná expanze a možnost autologního použití. MSC byly v posledních 15 letech studovány v experimentálním míšním poranění zejména u hlodavců se slibnými výsledky. Existuje několik mechanizmů, jakými působí MSC na míšní lézi. Především to je remyelinizace demyelinizovaných vláken, podpora pučení axonů (sprouting), angiogeneze, imunosupresivní efekt či sekrece neurotrofních faktorů, které mohou vést k funk­čnímu zlepšení. Tyto slibné výsledky urychlily zahájení klinických studií u pacientů s poraněním míchy. Klinické studie fáze I/II ukázaly, že se jedná o bezpečnou metodu, avšak funkční průkaz vyžaduje další klinické studie. Ukazuje se, že MSC bude třeba kombinovat s jinými metodami, jako je přemostění léze, enzymatické štěpení jizvy a blokátory inhibičních faktorů. Tato práce přináší přehledný souhrn o aplikaci MSC u míšního poranění v experimentu i klinice.

The use of mesenchymal stem cells (MSC) represents an experimental therapeutic modality in the treatment of spinal cord injury. MSC can be harvested from the bone marrow, fat tissue and other peripheral tissues from adult individuals. Compared to other types of stem cells, MSC are easy to access and expand and they can be used in autologous settings. Over the last 15 years, MSC have been widely studied in experimental spinal cord injury, especially in rodents, with promising results. MSC support remyelination of demyelinated axons, axonal sprouting, angiogenesis, have immunosuppressive effect and secrete neurotrophic factors that may led to functional improvement. These promising results led to launching of clinical studies in patients with spinal cord injury. Phase I/II clinical studies showed that the use of MSC represent a safe method. However, functional effect needs to be proved in further clinical studies. Data suggest that MSC will need to be combined with other methods, such as lesion bridging, scar tissue breakdown and blocking of inhibitory molecules. This paper provides an overview of the use of MSC in experimental and clinical SCI.

• Klíčová slova
• limitace studií, experimentální studie, intravenózní aplikace, intraarteriální aplikace, intratékální aplikace, intraspinální aplikace,
• MeSH
• axony fyziologie   patologie   MeSH
• buňky kostní dřeně cytologie   MeSH
• časové faktory MeSH
• Haplorrhini MeSH
• homologní transplantace MeSH
• injekce do léze MeSH
• intravenózní podání MeSH
• klinické zkoušky jako téma MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky * cytologie   metabolismus   MeSH
• mícha cytologie   patologie   účinky léků   MeSH
• modely u zvířat MeSH
• poranění míchy * terapie   MeSH
• regenerace nervu MeSH
• transplantace mezenchymálních kmenových buněk * metody   využití   MeSH
• transplantace mozkové tkáně metody   MeSH
• výsledek terapie MeSH
• výzkumný projekt MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy 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 suffer from complete loss of Purkinje cells and a reduction of granule cells and inferior olive neurons. Their wild type littermates serve as healthy controls. The aim of the work was to compare solid embryonic cerebellar graft survival within a period of 9 weeks after their transplantation in adult Lurcher mutant and wild type mice of the B6CBA strain. The solid grafts were injected through a hole in the occipital bone. Host mice were sacrificed 3, 6, or 9 weeks after the transplantation and their cerebella and brain-stems were examined histologically to assess graft presence and structure. We did not find significant differences in graft survival rates between Lurcher mutant and wild type mice. The frequency of graft presence did not differ between mice examined 3, 6, and 9 weeks after the transplantation, neither in Lurchers nor in wild type mice. The grafts were of various sizes. In some cases, only small residua of the grafts were found. Nerve fiber sprouting and cell migration from the graft to the host tissue were observed more often in wild type mice than in Lurchers when examined 6 weeks after surgery. In the period 3-9 weeks after transplantation, massive dying out of the grafts was not observed despite regressive processes in some of the grafts. The degenerative changes in the Lurcher mutant cerebellum do not have strong impact on the fate of the solid cerebellar graft. (c) 2009 Wiley-Liss, Inc.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• mozeček cytologie   embryologie   transplantace   MeSH
• myši - mutanty neurologické MeSH
• myši MeSH
• nemoci mozečku genetika   chirurgie   patofyziologie   MeSH
• neurodegenerativní nemoci genetika   chirurgie   patofyziologie   MeSH
• neurogeneze fyziologie   MeSH
• pilotní projekty MeSH
• pohyb buněk fyziologie   MeSH
• přežívání štěpu fyziologie   MeSH
• regenerace nervu fyziologie   MeSH
• růstové kužele fyziologie   ultrastruktura   MeSH
• transplantace mozkové tkáně metody   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

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

Terapie Huntingtonovy chorey je zatím jen velmi omezená. Neurální transplantace je nyní jediným léčebným zákrokem, kterým se u většiny pacientů dosáhne zmírnění projevů onemocnění, avšak časově omezeného. Další možností by, jak se zdá, mohla být stimulace proliferační aktivity v subependymální vrstvě (SEV) laterálních mozkových komor. SEV je zdrojem progenitorových buněk i v dospělosti. Naším záměrem je popsat reakci buněk v SEV u experimentálních zvířat. Chceme charakterizovat základní typy buněk v SVZa změny v jejich počtu. Předpokládá se, že k těmto změnám dochází v důsledku proliferace a degenerace (především apoptózou), navozené neurodegenerativním procesem ve striatu (neurotoxická léze) a následnou transplantací fetální nervové tkáně.; The therapy of Huntington's disease is very limited at the present time. Neural grafting is now the only therapeutic approach which provides a reduction of symptoms in most of the patients, but only temporarily. It seems that stimulation of proliferativeactivity within the subependymal layer (SEL] of the lateral brain ventricles may provide another alternative. The SEL is a source of progenitor cells even in adulthood. Our aim is to describe the SEL cell's reaction in the experimental animals. We wouldlike to characterize the basic types of cells within the SEL and the changes in their number. These changes are supposed to be caused by proliferation and degeneration (mostly by apoptosis), which is induced by the neurodegenerative process within the striatum (neurotoxic lesion) and by the following grafting of the fetal neural tissue.

• MeSH
• apoptóza MeSH
• chromozomální poruchy MeSH
• Huntingtonova nemoc chirurgie   terapie   MeSH
• imunohistochemie MeSH
• neurochirurgie metody   trendy   MeSH
• striatonigrální degenerace MeSH
• transplantace mozkové tkáně MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• neurochirurgie
• cytologie, klinická cytologie
• genetika, lékařská genetika
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• MeSH
• experimenty na zvířatech statistika a číselné údaje   MeSH
• finanční podpora výzkumu jako téma MeSH
• myši - mutanty neurologické genetika   MeSH
• nemoci mozečku MeSH
• orientace MeSH
• plavání MeSH
• transplantace mozkové tkáně patologie   MeSH
• vnímání prostoru MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH