ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 62 citations in OpenAlex.
- Effect of P-glycoprotein inhibition at the blood-brain barrier on brain distribution of (R)-[British journal of clinical pharmacology · 2017Trial
- Interaction of 11C-tariquidar and 11C-elacridar with P-glycoprotein and breast cancer resistance protein at the human blood-brain barrier.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2013Trial
- Simulation-based assessment of the P-glycoprotein expression-activity relationship shows a drug and system dependency.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Preclinical PET imaging in epileptogenesis: towards identification of biomarkers and therapeutic targets.EJNMMI research · 2025Review
- [Fluids and barriers of the CNS · 2024Article
- St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.Clinical and translational science · 2024Article
- [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Impact of Cytochrome Induction or Inhibition on the Plasma and Brain Kinetics of [Pharmaceutics · 2022Article
- Secondary Epileptogenesis: Common to See, but Possible to Treat?Frontiers in neurology · 2021Review
- Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model.International journal of molecular sciences · 2020Article
- Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?Pharmaceutics · 2020Review
- Age dependency of cerebral P-glycoprotein function in wild-type and APPPS1 mice measured with PET.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Neuroimaging Biomarkers of Experimental Epileptogenesis and Refractory Epilepsy.International journal of molecular sciences · 2019Review
- Age-associated physiological and pathological changes at the blood-brain barrier: A review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Review
- Recent Advances in Radiotracer Imaging Hold Potential for Future Refined Evaluation of Epilepsy in Veterinary Neurology.Frontiers in veterinary science · 2017Review
- Intercellular transfer of P-glycoprotein in human blood-brain barrier endothelial cells is increased by histone deacetylase inhibitors.Scientific reports · 2016Article
- Role of (drug) transporters in imaging in health and disease.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
- Workshop on Neurobiology of Epilepsy appraisal: new systemic imaging technologies to study the brain in experimental models of epilepsy.Epilepsia · 2014Article
- Neuropathology of the blood-brain barrier in epilepsy: support to the transport hypothesis of pharmacoresistance.Epilepsy currents · 2013Article
- Advances in PET imaging of P-glycoprotein function at the blood-brain barrier.ACS chemical neuroscience · 2013Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Approximately one-third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood-brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate (R)-[(11)C]verapamil and different doses of coadministered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood-brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of (R)-[(11)C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k(2), but not in distribution volume V(T) or influx rate constant K(1), correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.