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: Contribution to journalArticlepeer-review

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 μs) 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 DOT-analysis after semiautomatic coregistration to an average MRI pig brain. Results: rCBF was significantly increased (tvalue = 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, p-value < 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)
Pages (from-to)309-325
Number of pages17
JournalBrain Research Journal
Volume5
Issue number3-4
StatePublished - Sep 2012

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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