title: Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents.
abstract: Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson's disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft-host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions.
authors: University Freiburg Medical Center, Freiburg im Breisgau, Germany luciano.furlanetti@uniklinik-freiburg.de.
authors: Luciano L
authors: LL
authors: Furlanetti
authors: University Freiburg Medical Center, Freiburg im Breisgau, Germany.
authors: Joacir Graciolli
authors: JG
authors: Cordeiro
authors: University Freiburg Medical Center, Freiburg im Breisgau, Germany.
authors: Karina Kohn
authors: KK
authors: Cordeiro
authors: University Freiburg Medical Center, Freiburg im Breisgau, Germany Columbia University, New York, NY, USA.
authors: Joanna A
authors: JA
authors: García
authors: University Freiburg Medical Center, Freiburg im Breisgau, Germany Lindenbrunn Hospital, Coppenbrügge, Germany.
authors: Christian
authors: C
authors: Winkler
authors: University of São Paulo, São Paulo, Brazil University of Tübingen, Tübingen, Germany.
authors: Guilherme A
authors: GA
authors: Lepski
authors: University Freiburg Medical Center, Freiburg im Breisgau, Germany.
authors: Volker A
authors: VA
authors: Coenen
authors: University Hospital of Erlangen, Erlangen, Germany.
authors: Guido
authors: G
authors: Nikkhah
authors: University Freiburg Medical Center, Freiburg im Breisgau, Germany.
authors: Máté D
authors: MD
authors: Döbrössy
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000502:physiology* / Q000637:transplantation; D053331:Ectodysplasins / Q000378:metabolism; D004622:Embryo, Mammalian; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000628:therapy*; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D020531:Subthalamic Nucleus / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D053331:Ectodysplasins; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: 6-hydroxydopamine; Parkinson’s disease; cell therapy; deep brain stimulation; subthalamic nucleus