A novel strategy for intrastriatal dopaminergic cell transplantation: sequential "nest" grafting influences survival and behavioral recovery in a rat model of Parkinson's disease.
Exp Cell Res
; 318(20): 2531-42, 2012 Dec 10.
Article
en En
| MEDLINE
| ID: mdl-23010385
ABSTRACT
Neural transplantation in experimental parkinsonism (PD) is limited by poor survival of grafted embryonic dopaminergic (DA) cells. In this proof-of-principle study we hypothesized that a first regular initial graft may create a "dopaminergic" environment similar to the perinatal substantia nigra and consequently stimulate a subsequent graft. Therefore, we grafted ventral mesencephalic neurons sequentially at different time intervals into the same target localization. Rats with a unilateral lesion of the dopamine neurons produced by injections of 6-hydroxydopamine (6-OHDA) received E14 ventral mesencephalon derived grafts into the DA-depleted striatum. In the control group we grafted all 6 deposits on the first day (d0). The other 4 groups received four graft deposits distributed over 2 implantation tracts followed by a second engraftment injected into the same site 3, 6, 14 and 21 days later. Quantitative assessment of the survival of tyrosine hydroxylase-immunoreactive neurons and graft volume revealed best results for those DA grafts implanted 6 days after the first one. In the present study, a model of short-interval sequential transplantation into the same target-site, so called "nest" grafts were established in the 6-OHDA rat model of PD which might become a useful tool to further elucidate the close neurotrophic and neurotopic interactions between the immediate graft vicinity and the cell suspension graft. In addition, we could show that the optimal milieu was established around the sixth day after the initial transplantation. This may also help to further optimize current transplantation strategies to restore the DA system in patients with PD.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Conducta Animal
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Trasplante de Células
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Cuerpo Estriado
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Recuperación de la Función
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Trastornos Parkinsonianos
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Neuronas Dopaminérgicas
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Supervivencia de Injerto
Límite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
Alemania