Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:268 |
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| Enthalten in: |
Journal of neurology - 268(2021), 6 vom: 12. Juni, Seite 2246-2255 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fujita, Koji [VerfasserIn] |
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| Links: |
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| Themen: |
46627O600J |
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| Anmerkungen: |
Date Completed 18.06.2021 Date Revised 18.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00415-021-10411-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32064345X |
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| 100 | 1 | |a Fujita, Koji |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia |
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| 500 | |a Date Completed 18.06.2021 | ||
| 500 | |a Date Revised 18.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: 82Rb PET did not reveal significant changes in BBB permeability in PD patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Blood–brain barrier | |
| 650 | 4 | |a Levodopa-induced dyskinesia | |
| 650 | 4 | |a PET | |
| 650 | 4 | |a Parkinson’s disease | |
| 650 | 4 | |a Rubidium-82 | |
| 650 | 7 | |a Antiparkinson Agents |2 NLM | |
| 650 | 7 | |a Levodopa |2 NLM | |
| 650 | 7 | |a 46627O600J |2 NLM | |
| 700 | 1 | |a Peng, Shichun |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Yilong |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Chris C |e verfasserin |4 aut | |
| 700 | 1 | |a Hellman, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Feigin, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Eidelberg, David |e verfasserin |4 aut | |
| 700 | 1 | |a Dhawan, Vijay |e verfasserin |4 aut | |
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