title: Brain Tissue Reaction to Deep Brain Stimulation-A Longitudinal Study of DBS in the Goettingen Minipig.
abstract: OBJECTIVE
  The use of Deep Brain Stimulation (DBS) in treatment of various brain disorders is constantly growing; however, the number of studies of the reaction of the brain tissue toward implanted leads is still limited. Therefore, the aim of our study was to analyze the impact of DBS leads on brain tissue in a large animal model using minipigs.
  
  
  METHODS
  Twelve female animals, one control and eleven with bilaterally implanted DBS electrodes were used in our experiment. 3, 6, and 12 months after implantation the animals were sacrificed, perfused and the brains were removed. Tissue blocks containing the lead tracks were dissected, frozen, sectioned into 40 µm sections and stained using Nissl and Eosin, anti-GFAPab or Isolectin. The tissue reaction was analyzed at five levels, following from the distal lead tip, to compare tissue response in stimulated and nonstimulated areas: four segments along each level of electrodes, and the fifth level lying outside the electrode area (control area). The sections were described both qualitatively and quantitatively. Quantitative assessment of the reaction to the implanted electrode was based on the measurement of the area covered by the staining and the thickness of the glial scar.
  
  
  CONCLUSIONS
  Tissue reaction was, on average, limited to distance of 500 μm from the lead track. The tissue response after 12 months was weaker than after 6 months confirming that it stabilizes over a time. There was no histological evidence that the stimulated part of the electrode triggered different tissue response than its nonstimulated part.
authors.affiliation: CENSE group, Department of Neurosurgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Dariusz
authors.identifier: http://orcid.org/0000-0002-9542-402X
authors.initials: D
authors.lastname: Orlowski
authors.affiliation: Aleva Neurotherapeutics SA, Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Michalis
authors.affiliation: CENSE group, Department of Neurosurgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Glud
authors.affiliation: CENSE group, Department of Neurosurgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Anders R
authors.initials: AR
authors.lastname: Korshøj
authors.affiliation: CENSE group, Department of Neurosurgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Lise M
authors.initials: LM
authors.lastname: Fitting
authors.affiliation: CENSE group, Department of Neurosurgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Trine W
authors.initials: TW
authors.lastname: Mikkelsen
authors.affiliation: Aleva Neurotherapeutics SA, Lausanne, Switzerland.
authors.forename: André
authors.initials: A
authors.lastname: Mercanzini
authors.affiliation: Aleva Neurotherapeutics SA, Lausanne, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Jordan
authors.affiliation: Aleva Neurotherapeutics SA, Lausanne, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Dransart
authors.affiliation: CENSE group, Department of Neurosurgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Jens C H
authors.initials: JCH
authors.lastname: Sørensen
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000601:surgery*; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000295:instrumentation / Q000639:trends*; D004567:Electrodes, Implanted / Q000009:adverse effects / Q000639:trends*; D005260:Female; D008137:Longitudinal Studies; D013552:Swine; D013556:Swine, Miniature
keywords: animal models; deep brain stimulation; histology; inflammation; minipig