Substitution of lost neurons by neurotransplantation would be a possible management of advanced degenerative cerebellar ataxias in which insufficient cerebellar reserve remains. In this study, we examined the volume and structure of solid embryonic cerebellar grafts in adult Lurcher mice, a model of olivocerebellar degeneration, and their healthy littermates. Grafts taken from enhanced green fluorescent protein (EGFP)-positive embryos were injected into the cerebellum of host mice. Two or six months later, the brains were examined histologically. The grafts were identified according to the EGFP fluorescence in frozen sections and their volumes were estimated using the Cavalieri principle. For gross histological evaluation, graft-containing slices were processed using Nissl and hematoxylin-eosin staining. Adjustment of the volume estimation approach suggested that it is reasonable to use all sections without sampling, but that calculation of values for up to 20% of lost section using linear interpolation does not constitute substantial error. Mean graft volume was smaller in Lurchers than in healthy mice when examined 6 months after the transplantation. We observed almost no signs of graft destruction. In some cases, compact grafts disorganized the structure of the host's cerebellar cortex. In Lurchers, the grafts had a limited contact with the host's cerebellum. Also, graft size was of greater variability in Lurchers than in healthy mice. The results are in compliance with our previous findings that Lurcher phenotype-associated factors have a negative effect on graft development. These factors can hypothetically include cerebellar morphology, local tissue milieu, or systemic factors such as immune system abnormalities.

Department of Biology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Histology and Embryology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Medical Chemistry and Biochemistry Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Neurology Faculty Hospital in Pilsen and Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Pathophysiology Faculty of Medicine in Pilsen Charles University Alej Svobody 76 323 00 Plzen Czech Republic

Department of Physiology Anatomy and Cellular Biology Pablo de Olavide University Seville Spain

Laboratory of Neurodegenerative Disorders Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Laboratory of Quantitative Histology Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

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Lurcher Mouse as a Model of Cerebellar Syndromes