ArticlePloS one2014
In vivo measurement of hippocampal GABAA/cBZR density with [18F]-flumazenil PET for the study of disease progression in an animal model of temporal lobe epilepsy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Effects of cell therapy on seizures in animal models of epilepsy: Systematic review and meta-analysis.Epilepsia · 2026Pooled it
- Preclinical PET imaging in epileptogenesis: towards identification of biomarkers and therapeutic targets.EJNMMI research · 2025Review
- Local depletion of large molecule drugs due to target binding in tissue interstitial space.CPT: pharmacometrics & systems pharmacology · 2024Review
- Identification of the Hepatic Metabolites of Flumazenil and their Kinetic Application in Neuroimaging.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Automated Synthesis of [Pharmaceuticals (Basel, Switzerland) · 2023Article
- Effective Preparation of [Molecules (Basel, Switzerland) · 2022Article
- Recent Developments in Diagnosis of Epilepsy: Scope of MicroRNA and Technological Advancements.Biology · 2021Review
- Update on the Neuroimaging and Electroencephalographic Biomarkers of Epileptogenesis: A Literature Review.Frontiers in neurology · 2021Review
- Neuroimaging Biomarkers of Experimental Epileptogenesis and Refractory Epilepsy.International journal of molecular sciences · 2019Review
- Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology.Frontiers in neurology · 2017Article
- In Vivo Imaging of Human Neuroinflammation.ACS chemical neuroscience · 2016Review
- Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors.Current topics in medicinal chemistry · 2016Review
- Effect of (+)-dehydrofukinone on GABAA receptors and stress response in fish model.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2016Article
- Blood-brain barrier permeability and brain uptake mechanism of kainic acid and dihydrokainic acid.Neurochemical research · 2015Article
- Workshop on Neurobiology of Epilepsy appraisal: new systemic imaging technologies to study the brain in experimental models of epilepsy.Epilepsia · 2014Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeImbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [(18)F]-flumazenil ([(18)F]-FMZ) PET could be used to non-invasively characterise GABAA/central benzodiazepine receptor (GABAA/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE.
methodsDynamic [(18)F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM). SE was induced in eight male Wistar rats (10 weeks of age) by i.p. injection of kainic acid (7.5-25 mg/kg), while control rats (n = 7) received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [(18)F]-FMZ PET scan (3.6-4.6 nmol). The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [(18)F]-FMZ PET data. KEY
findingsThe PSM was found to adequately model [(18)F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01), accompanied by an increase in apparent affinity (p<0.05) compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05), but did not correlate with [(18)F]-FMZ binding. SIGNIFICANCE: Alterations to hippocampal GABAA/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [(18)F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [(18)F]-FMZ PET is useful for investigating the role that changes GABAA/cBZR density and binding affinity play in the pathogenesis of TLE.
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