Abstract
BackgroundDeep 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).ResultsNineteen 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0077-4) contains supplementary material, which is available to authorized users.
Highlights
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)
Methods to collect samples should be standardized and sampling-to-freezer time should be kept as short as possible. While this may seem unrealistic at first glance, we propose a novel strategy to obtain PD-relevant samples that may approximate these requirements, based on the concept of in vivo brain tissue imprinting during electrode implantation for deep brain stimulation (DBS) [21]
We demonstrate for the first time the feasibility, safety, and scientific interest of collecting and studying such DBS-associated samples, here referred to as brain tissue imprints (BTIs), which may provide unique biological signatures of deep brain structures, and, in our opinion, may represent a new paradigm in PD research using highly relevant brain material from living patients
Summary
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). Four decades of intensive research have proved yet unsuccessful at deciphering the aetiology and mechanisms underlying nigral decay in Parkinson’s disease (PD) [1,2,3], in spite of myriads of hypotheses that have been proposed far [4]. With few exceptions, post-mortem samples are obtained from patients at an advanced stage of disease, making it difficult to identify early molecular events at the basis of the complex basal ganglia (BG) electrophysiology and PD pathogenesis
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