Long-term immunosuppression for CNS mouse xenotransplantation: Effects on nigrostriatal neurodegeneration and neuroprotective carotid body cell therapy
| Autor: | Miriam Echevarría, Sonia Romo-Madero, Alfonso Bermejo-Navas, Roberto García-Swinburn, Nela Suárez-Luna, Juan José Toledo-Aral, Javier Villadiego |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Parkinson's disease Xenotransplantation medicine.medical_treatment Dopamine Immunology Transplantation Heterologous Cell- and Tissue-Based Therapy Pharmacology Neuroprotection Cell therapy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Immunosuppression Therapy Neurons Transplantation Carotid Body business.industry Parkinsonism MPTP Neurodegeneration Immunosuppression medicine.disease Corpus Striatum Mice Inbred C57BL Disease Models Animal 030104 developmental biology chemistry Heterografts business 030217 neurology & neurosurgery |
| Zdroj: | Xenotransplantation. 25(6) |
| ISSN: | 1399-3089 |
| Popis: | Background The use of long-term immunosuppressive treatments on neural transplantation has been controversial during the last decades. Although nowadays there is a consensus about the necessity of maintaining a permanent state of immunosuppression to preserve the survival of cerebral grafts, little is known about the effects that chronic immunosuppression produces both on the neurodegenerative process and on transplants function. Methods Here, we establish a new immunosuppressive protocol, based on the discontinuous administration of CsA (15 mg/kg; s.c.) and prednisone (20 mg/kg; s.c.), to produce long-term immunosuppression in mice. Using this treatment, we analyse the effects that long-term immunosuppression induces in a chronic 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) model of parkinsonism and on the neuroprotective and neurorestorative anti-parkinsonian actions exerted by rat carotid body (CB) xenografts. Results This protocol preserves the survival of rat CB xenotransplants maintaining the general wellness of the grafted mice. Although permanent immunosuppression does not prevent the MPTP-induced cell death of nigral neurons and the consequent degeneration of dopaminergic striatal innervation, allowing for its use as Parkinson's disease (PD) model, it reduces the microglial activation and slightly declines the striatal damage. Moreover, we reported that chronic administration of immunosuppressant drugs does not alter the neuroprotective and restorative anti-parkinsonian actions of rat CB xenografts into parkinsonian mice. Conclusions This new immunosuppressive protocol provides a new murine model to assay the long-term effects of cerebral xenografts and offer a pharmacological alternative to the commonly used genetic immunodeficient mice, allowing the use of genetically modified mice as hosts. In addition, it will permit the experimental analysis of the effects produced by human CB xenografts in the chronic PD murine model, with the final aim of using CB allografts as an option of cell therapy in PD patients. |
| Databáze: | OpenAIRE |
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