Most cited article - PubMed ID 27047666
Experimental neurotransplantation treatment for hereditary cerebellar ataxias
Restoration of damaged central nervous system structures, functional recovery, and prevention of neuronal loss during neurodegenerative diseases are major objectives in cerebellar research. The highly organized anatomical structure of the cerebellum with numerous inputs/outputs, the complexity of cerebellar functions, and the large spectrum of cerebellar ataxias render therapies of cerebellar disorders highly challenging. There are currently several therapeutic approaches including motor rehabilitation, neuroprotective drugs, non-invasive cerebellar stimulation, molecularly based therapy targeting pathogenesis of the disease, and neurotransplantation. We discuss the goals and possible beneficial mechanisms of transplantation therapy for cerebellar damage and its limitations and factors determining outcome.
- Keywords
- Ataxias, Cerebellar reserve, Cerebellum, Neurotransplantation, Stem cells,
- MeSH
- Cell- and Tissue-Based Therapy methods MeSH
- Cerebellar Diseases therapy MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review 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.
- Keywords
- Cerebellar degeneration, Cerebellum, Lurcher mouse, Purkinje cell, Transplantation,
- MeSH
- Species Specificity MeSH
- Longitudinal Studies MeSH
- Rotarod Performance Test MeSH
- Disease Models, Animal MeSH
- Motor Skills MeSH
- Cerebellum embryology pathology transplantation MeSH
- Mice, Neurologic Mutants MeSH
- Mice, Inbred C3H MeSH
- Mice, Inbred CBA MeSH
- Mice, Transgenic MeSH
- Cerebellar Diseases pathology physiopathology therapy MeSH
- Neurodegenerative Diseases pathology physiopathology therapy MeSH
- Graft Survival * physiology MeSH
- Brain Tissue Transplantation * MeSH
- Green Fluorescent Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- enhanced green fluorescent protein MeSH Browser
- Green Fluorescent Proteins MeSH