title: Increased precursor cell proliferation after deep brain stimulation for Parkinson's disease: a human study.
abstract: OBJECTIVE
  Deep brain stimulation (DBS) has been used for more than a decade to treat Parkinson's disease (PD); however, its mechanism of action remains unknown. Given the close proximity of the electrode trajectory to areas of the brain known as the "germinal niches," we sought to explore the possibility that DBS influences neural stem cell proliferation locally, as well as more distantly.
  
  
  METHODS
  We studied the brains of a total of 12 idiopathic Parkinson's disease patients that were treated with DBS (the electrode placement occurred 0.5-6 years before death), and who subsequently died of unrelated illnesses. These were compared to the brains of 10 control individuals without CNS disease, and those of 5 PD patients with no DBS.
  
  
  RESULTS
  Immunohistochemical analyses of the subventricular zone (SVZ) of the lateral ventricles, the third ventricle lining, and the tissue surrounding the DBS lead revealed significantly greater numbers of proliferating cells expressing markers of the cell cycle, plasticity, and neural precursor cells in PD-DBS tissue compared with both normal brain tissue and tissue from PD patients not treated with DBS. The level of cell proliferation in the SVZ in PD-DBS brains was 2-6 fold greater than that in normal and untreated PD brains.
  
  
  CONCLUSIONS
  Our data suggest that DBS is capable of increasing cellular plasticity in the brain, and we hypothesize that it may have more widespread effects beyond the electrode location. It is unclear whether these effects of DBS have any symptomatic or other beneficial influences on PD.
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America; Department of Neurology, UF Center for Movement Disorders and Restoration, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Vinata
authors.initials: V
authors.lastname: Vedam-Mai
authors.affiliation: Department of Anatomy with Radiology and Centre for Brain Research, School of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Bronwen
authors.initials: B
authors.lastname: Gardner
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America; Department of Neurology, UF Center for Movement Disorders and Restoration, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Florian A
authors.initials: FA
authors.lastname: Siebzehnrubl
authors.affiliation: Department of Anatomy with Radiology and Centre for Brain Research, School of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Monica
authors.initials: M
authors.lastname: Kam
authors.affiliation: Department of Anatomy with Radiology and Centre for Brain Research, School of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Palingu
authors.initials: P
authors.lastname: Aponso
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Steindler
authors.affiliation: Department of Pathology, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Yachnis
authors.affiliation: Department of Biostatistics, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Neal
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Brittany U
authors.initials: BU
authors.lastname: Oliver
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Rath
authors.affiliation: Department of Anatomy with Radiology and Centre for Brain Research, School of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
authors.affiliation: Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Reynolds
authors.affiliation: Department of Anatomy with Radiology and Centre for Brain Research, School of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Curtis
mesh_terms: D049109:Cell Proliferation; D046690:Deep Brain Stimulation; D006801:Humans; D007150:Immunohistochemistry; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*