title: Deep brain stimulation-associated brain tissue imprints: a new in vivo approach to biological research in human Parkinson's disease.
abstract: BACKGROUND
  Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) has been established as a highly effective symptomatic therapy for Parkinson's disease (PD). An intriguing biological aspect related to the DBS procedure is that a temporary contact establishes between surgical instruments and the surrounding brain tissue. In this exploratory study, we took advantage of this unique context to harvest brain material adhering to the stylet routinely used during surgery, and to examine the biological value of these samples, here referred to as "brain tissue imprints" (BTIs).
  
  
  RESULTS
  Nineteen BTIs from 12 STN- or GPi-electrode implanted patients were obtained in vivo during DBS surgery, without any modification of the surgical procedure. Immunofluorescence analyses confirmed that our approach allowed the harvesting of many neural cells including neurons harboring distinct neurotransmitter markers. Shotgun proteomic and transcriptomic analyses provided for the first time molecular information from DBS-associated brain samples, and confirmed the compatibility of this new type of sample with poly-omic approaches. The method appears to be safe and results consistent.
  
  
  CONCLUSIONS
  We here propose BTIs as original and highly valuable brain samples, and DBS-related brain imprinting as a new conceptual approach to biological research in living patients with PD.
authors.affiliation: NeuroProteomics Group, University Medical Center, Faculty of Medicine, Geneva, Switzerland. Affif.Zaccaria@unige.ch.|Centre Medical Universitaire (CMU), Rue Michel Servet 1, CH-1211, Genève 4, Switzerland. Affif.Zaccaria@unige.ch.
authors.forename: Affif
authors.initials: A
authors.lastname: Zaccaria
authors.affiliation: CEA-LETI, Clinatec, Edmond J. Safra Biomedical Research Center, Grenoble, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Bouamrani
authors.affiliation: Clinique de neurochirurgie, CHU de Grenoble, Grenoble, France.|Inserm, U836, Grenoble Institut des Neurosciences, Univ. Grenoble Alpes, Grenoble, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Chabardès
authors.affiliation: CEA-LETI, Clinatec, Edmond J. Safra Biomedical Research Center, Grenoble, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: El Atifi
authors.affiliation: Clinique de neurochirurgie, CHU de Grenoble, Grenoble, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Seigneuret
authors.affiliation: Department of Pathology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Lobrinus
authors.affiliation: Department of Pathology and Immunology, University Medical Center, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Dubois-Dauphin
authors.affiliation: Inserm UA01, Clinatec, Edmond J. Safra Biomedical Research Center, CEA, Grenoble CHU, Univ. Grenoble Alpes, Grenoble, France.
authors.forename: François
authors.initials: F
authors.lastname: Berger
authors.affiliation: NeuroProteomics Group, University Medical Center, Faculty of Medicine, Geneva, Switzerland.|Department of Neurology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Burkhard
mesh_terms: D000328:Adult; D000368:Aged; D046690:Deep Brain Stimulation; D005260:Female; D005917:Globus Pallidus; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D010300:Parkinson Disease / Q000628:therapy*; D040901:Proteomics; D020531:Subthalamic Nucleus
references.citation: Neurology. 2000;55(12 Suppl 6):S34-9
references.pmid: 11188973
references.citation: Nat Rev Neurosci. 2001 Aug;2(8):589-94
references.pmid: 11484002
references.citation: Expert Rev Neurother. 2010 Jun;10(6):925-42
references.pmid: 20518609
references.citation: Appl Neurophysiol. 1987;50(1-6):344-6
references.pmid: 3329873
references.citation: Fukushima J Med Sci. 2012;58(1):82-7
references.pmid: 22790897
references.citation: N Engl J Med. 2013 Feb 14;368(7):610-22
references.pmid: 23406026
references.citation: N Engl J Med. 1998 Oct 15;339(16):1130-43
references.pmid: 9770561
references.citation: Nat Genet. 2014 Sep;46(9):989-93
references.pmid: 25064009
references.citation: Biol Psychiatry. 2004 Feb 15;55(4):346-52
references.pmid: 14960286
references.citation: Lancet Neurol. 2009 Jan;8(1):67-81
references.pmid: 19081516
references.citation: Nature. 2006 Oct 19;443(7113):787-95
references.pmid: 17051205
references.citation: Brain Res. 2006 Dec 6;1123(1):1-11
references.pmid: 17045977
references.citation: J Neurol. 2001 Aug;248(8):695-700
references.pmid: 11569899
references.citation: J Proteomics. 2013 Feb 21;79:146-60
references.pmid: 23277275
references.citation: BMC Proc. 2009 Jul 16;3 Suppl 4:S6
references.pmid: 19615119
references.citation: N Engl J Med. 2008 Nov 13;359(20):2121-34
references.pmid: 19005196
references.citation: Lancet. 1991 Feb 16;337(8738):403-6
references.pmid: 1671433
references.citation: Neuroreport. 2005 Nov 28;16(17):1883-7
references.pmid: 16272872
references.citation: Prog Neurobiol. 2000 Sep;62(1):63-88
references.pmid: 10821982
references.citation: J Neuropathol Exp Neurol. 2008 Oct;67(10):923-32
references.pmid: 18800015
references.citation: Annu Rev Neurosci. 2006;29:229-57
references.pmid: 16776585
references.citation: Arch Pathol Lab Med. 2000 May;124(5):739-45
references.pmid: 10782159
references.citation: Epileptic Disord. 2002 Dec;4 Suppl 3:S83-93
references.pmid: 12495878
references.citation: Front Hum Neurosci. 2014 Sep 09;8:655
references.pmid: 25249957
references.citation: Annu Rev Neurosci. 2011;34:289-307
references.pmid: 21692660
references.citation: Parkinsons Dis. 2010 Dec 20;2011:658083
references.pmid: 21209719
references.citation: J Neuropathol Exp Neurol. 2007 Jan;66(1):35-46
references.pmid: 17204935
references.citation: Nat Rev Neurol. 2012 Sep;8(9):518-30
references.pmid: 22890216
references.citation: Annu Rev Neurosci. 1999;22:123-44
references.pmid: 10202534
references.citation: Neurosci Res. 1999 May;34(1):51-4
references.pmid: 10413327
references.citation: Expert Rev Proteomics. 2011 Jun;8(3):291-4
references.pmid: 21679108
references.citation: Lancet. 2011 Feb 19;377(9766):641-9
references.pmid: 21292315
references.citation: Lancet. 2004 May 29;363(9423):1783-93
references.pmid: 15172778
references.citation: Curr Opin Neurobiol. 2003 Dec;13(6):696-706
references.pmid: 14662371
references.citation: Brain Res Mol Brain Res. 2003 Oct 21;118(1-2):60-71
references.pmid: 14559355
references.citation: J Proteomics. 2009 Nov 2;73(1):10-29
references.pmid: 19632367
references.citation: Acta Neurochir (Wien). 2012 Nov;154(11):2069-74
references.pmid: 22814648
references.citation: Neurology. 2007 Jan 9;68(2):159-60
references.pmid: 17210901
references.citation: N Engl J Med. 1998 Oct 8;339(15):1044-53
references.pmid: 9761807