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Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

Authors

  • Karina Kohn Cordeiro,

    1. Department of Stereotactic and Functional Neurosurgery, Laboratory of Stereotaxy and Interventional Neurosciences, University Freiburg-Medical Center, Freiburg, Germany
    2. Federal University of Paraná, Hospital de Clínicas, Curitiba, Brazil
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  • Joacir Graciolli Cordeiro,

    1. Department of Stereotactic and Functional Neurosurgery, Laboratory of Stereotaxy and Interventional Neurosciences, University Freiburg-Medical Center, Freiburg, Germany
    2. Federal University of Paraná, Hospital de Clínicas, Curitiba, Brazil
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  • Luciano Lopes Furlanetti,

    1. Department of Stereotactic and Functional Neurosurgery, Laboratory of Stereotaxy and Interventional Neurosciences, University Freiburg-Medical Center, Freiburg, Germany
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  • Salazar Joanna Alejandra Garcia,

    1. Department of Neurology, University Freiburg-Medical Center, Freiburg, Germany
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  • Sérgio Bernardo Tenório,

    1. Federal University of Paraná, Hospital de Clínicas, Curitiba, Brazil
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  • Christian Winkler,

    1. Department of Neurology, University Freiburg-Medical Center, Freiburg, Germany
    2. Department of Neurology, Lindenbrunn Hospital, Coppenbrügge, Germany
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  • Máté Daniel Döbrössy,

    Corresponding author
    1. Department of Stereotactic and Functional Neurosurgery, Laboratory of Stereotaxy and Interventional Neurosciences, University Freiburg-Medical Center, Freiburg, Germany
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  • Guido Nikkhah

    1. Department of Neurosurgery, University Hospital of Erlangen, Erlangen, Germany
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  • K.K.C. and J.G.C. contributed equally to this study.

Abstract

Subthalamic nucleus (STN) modulation is currently the gold standard in the treatment of Parkinson's disease (PD) cases refractory to medication. Cell transplantation is a tissue-restorative approach and is a promising strategy in the treatment of PD. One of the obstacles to overcome in cell therapy is the poor dopaminergic cell survival. Our experiment investigates the impact of a partial subthalamotomy prior to ventral mesencephalic (VM) embryonic cell transplantation on dopaminergic cell survival and functional outcome. Unilateral dopamine depletion was carried out in rats, via medial forebrain bundle (MFB) injection of 6-hydroxydopamine, and half of the animals went on to receive unilateral excitotoxic lesions of the STN/Zone Incerta (ZI) causing partial lesion of these structures on the same side as the MFB lesion. All MFB-lesioned animals, with or without the STN/ZI lesion, received striatal ipsilateral embryonic VM cell grafts. The data suggest that the STN/ZI lesion could boost the dopamine cell survival in the grafts by 2.6-fold compared with the control grafted-only group. Moreover, performance on the drug-induced rotation and the spontaneous behavior tests were ameliorated on the STN/ZI-lesioned group to a significantly greater extent than the grafted-only group. These data suggest that the STN/ZI partial lesion optimized the striatal environment, promoting an improvement in cell survival. Further studies are needed to see whether the synergy between STN modulation via deep brain stimulation and cell therapy might have clinical applications in the management of PD.

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