title: Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study.
abstract: OBJECTIVE
  Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up-regulation of neural progenitor cell proliferation in post-mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, neural progenitor cells, and microglia.
  
  
  METHODS
  We used naïve rats in this study for DBS electrode implantation, stimulation, and microlesions. We used immunohistochemistry techniques for labeling microglial and progenitor cells, and fluorescence microscopy for viewing and quantification of labeled cells.
  
  
  RESULTS
  We present data that demonstrates a reciprocal relationship of microglia and neural precursor cells in the presence of acute high frequency stimulation. In our hands, stimulated animals demonstrate significantly lower numbers of activated microglia (p = 0.026) when compared to microlesion and sham animals. The subthalamic region surrounding the DBS stimulating electrode reveals a significant increase in the number of neural precursor cells expressing cell cycle markers, plasticity and precursor cell markers (Ki67; p = 0.0013, MCM2; p = 0.0002).
  
  
  CONCLUSIONS
  We conclude that in this animal model, acute DBS results in modest local progenitor cell proliferation and influenced the total number of activated microglia. This could be of clinical significance in patients with PD, as it is thought to progress via neuroinflammatory processes involving microglia, cytokines, and the complement system. Further studies are required to comprehend the behavior of microglia in different activation states and their ability to regulate adult neurogenesis under physiologic and pathologic conditions.
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of FL, Gainesville, FL, USA.|Department of Neurology, UF Center for Movement Disorders and Restoration, Gainesville, FL, USA.
authors.forename: Vinata
authors.initials: V
authors.lastname: Vedam-Mai
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of FL, Gainesville, FL, USA.
authors.forename: Massoud
authors.initials: M
authors.lastname: Baradaran-Shoraka
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of FL, Gainesville, FL, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Reynolds
authors.affiliation: Movement Disorders & Neurorestoration, Gainesville, FL, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000502:physiology; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000502:physiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D064111:Minichromosome Maintenance Complex Component 2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000166:cytology / Q000502:physiology*
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D064111:Minichromosome Maintenance Complex Component 2; D001973:Bromodeoxyuridine
keywords: Deep brain stimulation; Parkinson's disease; microglia; neural precursor cell; plasticity