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

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dc.contributor.authorVivash, Len_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorBouilleret, Ven_AU
dc.contributor.authorBerard, Aen_AU
dc.contributor.authorWimberley, CAen_AU
dc.contributor.authorBinns, Den_AU
dc.contributor.authorRoselt, Pen_AU
dc.contributor.authorKatsifis, Aen_AU
dc.contributor.authorMyers, DEen_AU
dc.contributor.authorHicks, RJen_AU
dc.contributor.authorO'Brien, TJen_AU
dc.contributor.authorDedeurwaerdere, Sen_AU
dc.date.accessioned2020-03-24T06:15:54Zen_AU
dc.date.available2020-03-24T06:15:54Zen_AU
dc.date.issued2014-01-21en_AU
dc.description.abstractPurpose Imbalance 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 [18F]-flumazenil ([18F]-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. Methods Dynamic [18F]-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 [18F]-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 [18F]-FMZ PET data. Key Findings The PSM was found to adequately model [18F]-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 [18F]-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 [18F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [18F]-FMZ PET is useful for investigating the role that changes GABAA/cBZR density and binding affinity play in the pathogenesis of TLE. © 2014 Vivash et al.en_AU
dc.identifier.citationVivash, L., Grégoire, M. C., Bouilleret, V., Berard, A., Wimberley, C., Binns, D., Rosel, P., Katsifis, A., Myers, D. E., Hicks, R. J. & O'Brien, T. J. (2014). 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. PloS one, 9(1), e86722. doi:10.1371/journal.pone.0086722en_AU
dc.identifier.govdoc8897en_AU
dc.identifier.issn1932-6203en_AU
dc.identifier.issue1en_AU
dc.identifier.journaltitlePloS oneen_AU
dc.identifier.paginatione86722en_AU
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0086722en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9222en_AU
dc.identifier.volume9en_AU
dc.language.isoenen_AU
dc.publisherPublic Library of Scienceen_AU
dc.subjectHippocampusen_AU
dc.subjectMagnetic resonanceen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectEpilepsyen_AU
dc.subjectElectroencephalographyen_AU
dc.subjectIn vivoen_AU
dc.subjectReceptorsen_AU
dc.subjectBlooden_AU
dc.subjectSimulationen_AU
dc.titleIn vivo measurement of hippocampal GABAA/cBZR density with [18F]-Flumazenil PET for the study of disease progression in an animal model of temporal lobe epilepsyen_AU
dc.typeJournal Articleen_AU
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