OBJECTIVE: Recent studies on a rodent model of Parkinson's disease (PD) have raised the possibility of increased blood-brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in human PD patients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID). METHODS: We used rubidium-82 (82Rb) and PET to quantify BBB influx in vivo in 19 PD patients, including eight with LID, and 12 age- and sex-matched healthy subjects. All subjects underwent baseline 82Rb scans. Seventeen chronically levodopa-treated patients were additionally rescanned during intravenous levodopa infusion. Influx rate constant, K1, by compartmental modeling or net influx transport, Ki, by graphical approach could not be estimated reliably. However, Vd, the "apparent volume of distribution" based on the 82Rb concentration in brain tissue and blood, was estimated with good stability as a local measure of the volume of distribution. RESULTS: Rubidium influx into brain tissue was undetectable in PD patients with or without LID, scanned on and off drug. No significant differences in regional Vd were observed for PD patients with or without LID relative to healthy subjects, except in left thalamus. Moreover, changes in Vd measured off- and on-levodopa infusion were also not significant for dyskinetic and non-dyskinetic subjects. CONCLUSION: 82Rb PET did not reveal significant changes in BBB permeability in PD patients.
OBJECTIVE: Recent studies on a rodent model of Parkinson's disease (PD) have raised the possibility of increased blood-brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in humanPDpatients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID). METHODS: We used rubidium-82 (82Rb) and PET to quantify BBB influx in vivo in 19 PDpatients, including eight with LID, and 12 age- and sex-matched healthy subjects. All subjects underwent baseline 82Rb scans. Seventeen chronically levodopa-treated patients were additionally rescanned during intravenous levodopa infusion. Influx rate constant, K1, by compartmental modeling or net influx transport, Ki, by graphical approach could not be estimated reliably. However, Vd, the "apparent volume of distribution" based on the 82Rb concentration in brain tissue and blood, was estimated with good stability as a local measure of the volume of distribution. RESULTS:Rubidium influx into brain tissue was undetectable in PDpatients with or without LID, scanned on and off drug. No significant differences in regional Vd were observed for PDpatients with or without LID relative to healthy subjects, except in left thalamus. Moreover, changes in Vd measured off- and on-levodopa infusion were also not significant for dyskinetic and non-dyskinetic subjects. CONCLUSION: 82Rb PET did not reveal significant changes in BBB permeability in PDpatients.
Authors: V Dhawan; T Ishikawa; C Patlak; T Chaly; W Robeson; A Belakhlef; C Margouleff; F Mandel; D Eidelberg Journal: J Nucl Med Date: 1996-02 Impact factor: 10.057
Authors: Vincent A Jourdain; Chris C Tang; Florian Holtbernd; Christian Dresel; Yoon Young Choi; Yilong Ma; Vijay Dhawan; David Eidelberg Journal: JCI Insight Date: 2016-09-22
Authors: Renata P Lerner; Veronica Francardo; Koji Fujita; Zisis Bimpisidis; Vincent A Jourdain; Chris C Tang; Stephen L Dewey; Thomas Chaly; M Angela Cenci; David Eidelberg Journal: Sci Rep Date: 2017-11-22 Impact factor: 4.379