Altered GABA A receptor density and unaltered blood-brain barrier [11C]flumazenil transport in drug-resistant epilepsy patients with mesial temporal sclerosis
| Autor: | Jaap C. Reijneveld, Robert C. Schuit, Ronald Boellaard, Maqsood Yaqub, N. Harry Hendrikse, Jan J. Heimans, Patrick Schober, Andrey Postnov, Esther Bakker, Femke E. Froklage, Adriaan A. Lammertsma, Emile F.I. Comans, Demetrios N. Velis, Rob A. Voskuyl, Jack Zwemmer |
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| Přispěvatelé: | Radiation Oncology, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Anesthesiology, Neurology, Neurosurgery, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, ACS - Microcirculation, APH - Quality of Care, APH - Methodology |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Flumazenil 0301 basic medicine positron emission tomography Adolescent Tariquidar Drug Resistance Hippocampus P-glycoprotein Pharmacology Blood–brain barrier Young Adult 03 medical and health sciences Epilepsy 0302 clinical medicine medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Carbon Radioisotopes GABA Modulators Volume of distribution Sclerosis GABAA receptor business.industry Binding potential Original Articles temporal lobe epilepsy Middle Aged Receptors GABA-A medicine.disease 030104 developmental biology medicine.anatomical_structure Epilepsy Temporal Lobe Neurology Blood-Brain Barrier Positron-Emission Tomography Neurology (clinical) Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Cerebral Blood Flow and Metabolism, 37(1), 97-105. Nature Publishing Group Froklage, F E, Postnov, A, Yaqub, M M, Bakker, E, Boellaard, R, Harry Hendrikse, N, Comans, E F I, Schuit, R C, Schober, P, Velis, D N, Zwemmer, J, Heimans, J J, Lammertsma, A A, Voskuyl, R A & Reijneveld, J C 2017, ' Altered GABA A receptor density and unaltered blood-brain barrier [ 11 C]flumazenil transport in drug-resistant epilepsy patients with mesial temporal sclerosis ', Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 1, pp. 97-105 . https://doi.org/10.1177/0271678X15618219 Journal of Cerebral Blood Flow & Metabolism |
| ISSN: | 0271-678X |
| DOI: | 10.1177/0271678X15618219 |
| Popis: | Studies in rodents suggest that flumazenil is a P-glycoprotein substrate at the blood–brain barrier. This study aimed to assess whether [11C]flumazenil is a P-glycoprotein substrate in humans and to what extent increased P-glycoprotein function in epilepsy may confound interpretation of clinical [11C]flumazenil studies used to assess gamma-aminobutyric acid A receptors. Nine drug-resistant patients with epilepsy and mesial temporal sclerosis were scanned twice using [11C]flumazenil before and after partial P-glycoprotein blockade with tariquidar. Volume of distribution, nondisplaceable binding potential, and the ratio of rate constants of [11C]flumazenil transport across the blood–brain barrier (K1/k2) were derived for whole brain and several regions. All parameters were compared between pre- and post-tariquidar scans. Regional results were compared between mesial temporal sclerosis and contralateral sides. Tariquidar significantly increased global K1/k2 (+23%) and volume of distribution (+10%), but not nondisplaceable binding potential. At the mesial temporal sclerosis side volume of distribution and nondisplaceable binding potential were lower in hippocampus (both ∼−19%) and amygdala (both ∼−16%), but K1/k2 did not differ, suggesting that only regional gamma-aminobutyric acid A receptor density is altered in epilepsy. In conclusion, although [11C]flumazenil appears to be a (weak) P-glycoprotein substrate in humans, this does not seem to affect its role as a tracer for assessing gamma-aminobutyric acid A receptor density. |
| Databáze: | OpenAIRE |
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