Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine parkinson model

Mette S. Nielsen, Flemming Andersen, Paul Cumming, Arne Møller, Albert Gjedde, Jens C. Sørensen, Carsten R. Bjarkam

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Background: Subthalamic high-frequency deep brain stimulation (STN DBS) has during the last decade been widely used in the treatment of Parkinson's disease (PD) complicated by motor fluctuations and medicine-induced adverse effects. The exact mechanism of STN DBS is, however, still unelucidated. Objective: To evaluate whether STN DBS changes regional cerebral blood flow (rCBF) and oxygen consumption, by positron emission tomography (PET) in a non-primate large animal PD model of STN DBS. Methods: Three MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intoxicated female Göttingen minipigs (age 8-12 months, weight 16-20 kg) were stereotaxically implanted unilaterally with a DBS electrode (Medtronic, model 3387) connected to a pulse generator (Medtronic, model 7424) placed subcutaneously in the neck region. Four to six weeks later the animals were anesthetized and placed in a PET scanner. Three water (H2 15O) and three oxygen (15O2) scans were performed, before stimulation with clinical parametres (continuous unipolar stimulation (electrode negative, case positive), amplitude 3V, frequency 160 Hz, and pulse-width 60 s) was initiated and followed by 5 water and oxygen scans 5, 30, 60, 120 and 240 min thereafter. The obtained data (the three baseline scans versus the five poststimulation scans) were analysed by parametric DOTanalysis after semiautomatic coregistration to an average MRI pig brain. Results: rCBF was significantly increased (t-value = 5.47, p-value < 0.05) at the electrode tip after initiation of stimulation, and non-significant increases of oxygen consumption occurred in the ipsilateral-(t-value = 3.67, p-value < 0.1), and contralateral cortex (t-value = 3.34, pvalue < 0.1). Conclusion: Our results indicate that STN DBS increases local midbrain rCBF and oxygen consumption in centrally placed cortical areas. The minipig may thus be a well-suited animal model for further studies of the mechanism of STN DBS in PD.

Original languageEnglish (US)
Title of host publicationDeep Brain Stimulation
Subtitle of host publicationApplications, Complications and Side Effects
PublisherNova Science Publishers, Inc.
Pages163-176
Number of pages14
ISBN (Print)9781606928950
StatePublished - Dec 1 2009

Keywords

  • Animal model
  • Basal ganglia
  • Cerebral oxygen consumption
  • Göttingen minipig
  • MPTP
  • Regional cerebral blood flow (rCBF)

ASJC Scopus subject areas

  • Psychology(all)
  • Medicine(all)

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    Nielsen, M. S., Andersen, F., Cumming, P., Møller, A., Gjedde, A., Sørensen, J. C., & Bjarkam, C. R. (2009). Subthalamic high-frequency deep brain stimulation evaluated by positron emission tomography in a porcine parkinson model. In Deep Brain Stimulation: Applications, Complications and Side Effects (pp. 163-176). Nova Science Publishers, Inc..