4.3 Article

Brain Tissue Reaction to Deep Brain StimulationA Longitudinal Study of DBS in the Goettingen Minipig

Journal

NEUROMODULATION
Volume 20, Issue 5, Pages 417-423

Publisher

WILEY
DOI: 10.1111/ner.12576

Keywords

animal models; deep brain stimulation; histology; inflammation; minipig

Funding

  1. Aleva Neurotherapeutics
  2. Clinical Institute, Aarhus University

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ObjectivesThe 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. MethodsTwelve 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 mu m 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. Results and Conclusions: Tissue reaction was, on average, limited to distance of 500 m 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.

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