In vivo P-glycoprotein function before and after epilepsy surgery

被引：39

作者：

Bauer, Martin ^{[1
]}

Karch, Rudolf ^{[3
]}

Zeitlinger, Markus ^{[1
]}

Liu, Joan ^{[6
]}

Koepp, Matthias J. ^{[6
,7
]}

Asselin, Marie-Claude ^{[8
]}

Sisodiya, Sanjay M. ^{[6
,7
]}

Hainfellner, Johannes A. ^{[4
]}

Wadsak, Wolfgang ^{[5
]}

Mitterhauser, Markus ^{[5
]}

Mueller, Markus ^{[1
]}

Pataraia, Ekaterina ^{[2
]}

Langer, Oliver ^{[9
]}

机构：

[1] Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria

[2] Med Univ Vienna, Dept Neurol, Vienna, Austria

[3] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Vienna, Austria

[4] Med Univ Vienna, Inst Neurol, Vienna, Austria

[5] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Div Nucl Med, Vienna, Austria

[6] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London, England

[7] Epilepsy Soc, Gerrards Cross, Bucks, England

[8] Univ Manchester, MAHSC, Inst Populat Hlth, Wolfson Mol Imaging Ctr, Manchester M13 9PL, Lancs, England

[9] AIT Austrian Inst Technol GmbH, Hlth & Environm Dept, Seibersdorf, Austria

来源：

NEUROLOGY | 2014年 / 83卷 / 15期

基金：

奥地利科学基金会;

关键词：

TEMPORAL-LOBE EPILEPSY; BLOOD-BRAIN-BARRIER; DRUG-RESISTANCE; PHARMACORESISTANCE; EXPRESSION; PROPOSAL;

D O I：

10.1212/WNL.0000000000000858

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Objectives: To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier of patients with temporal lobe epilepsy using (R)-[C-11] verapamil (VPM)-PET before and after temporal lobe surgery to assess whether postoperative changes in seizure frequency and antiepileptic drug load are associated with changes in Pgp function. Methods: Seven patients with drug-resistant temporal lobe epilepsy underwent VPM-PET scans pre- and postsurgery. Patients were followed up for a median of 6 years (range 4-7) after surgery. Pgp immunoreactivity in surgically resected hippocampal specimens was determined with immunohistochemistry. Results: Optimal surgical outcome, defined as seizure freedom and withdrawal of antiepileptic drugs, was associated with higher temporal lobe Pgp function before surgery, higher Pgp-positive staining in surgically resected hippocampal specimens, and reduction in global Pgp function postoperatively, compared with nonoptimal surgery outcome. Conclusions: The data from our pilot study suggest that Pgp overactivity in epilepsy is dynamic, and complete seizure control and elimination of antiepileptic medication is associated with reversal of overactivity, although these findings will require confirmation in a larger patient cohort.

引用

页码：1326 / 1331

页数：6

共 13 条

[1]

Pgp-Mediated Interaction Between (R)-[11C]Verapamil and Tariquidar at the Human Blood-Brain Barrier: A Comparison With Rat Data [J].