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Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

ABSTRACT: PURPOSE:The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. PROCEDURES:Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n?=?5) or kainic acid (5 mg/kg/injection, epileptic group, n?=?15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. RESULTS:Control rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p?

SUBMITTER: Serrano ME

PROVIDER: S-EPMC7497718 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Exploring with [<sup>18</sup>F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

Serrano Maria Elisa ME Bahri Mohamed Ali MA Becker Guillaume G Seret Alain A Germonpré Charlotte C Lemaire Christian C Giacomelli Fabrice F Mievis Frédéric F Luxen André A Salmon Eric E Rogister Bernard B Raedt Robrecht R Plenevaux Alain A

Molecular imaging and biology 20201001 5

<h4>Purpose</h4>The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model.<h4>Procedures</h4>Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE ...[more]

PMID: 32206990

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Project description:Objective:Reproductive dysfunction is a comorbidity that commonly occurs with temporal lobe epilepsy (TLE). Characterization of this comorbidity in various models of TLE in mice will greatly facilitate mechanistic investigations of the relationship between reproductive disorders and seizures initiated in the hippocampus. Here we investigate the impact on female reproductive estrous cyclicity in the intrahippocampal kainic acid mouse model of TLE and demonstrate the utility of using this model for future mechanistic studies. Methods:Kainic acid (KA) or saline vehicle was stereotaxically injected in the right dorsal hippocampus of adult female C57BL/6J mice. Development of epilepsy was assessed by video monitoring for behavioral seizures. Reproductive function was assessed by daily estrous cycle monitoring and ovarian morphology. Estrous cycles were monitored for up to 2 months after injection. Ovarian morphology was examined by histological staining and assessment of follicular and luteal development. Results:We observed spontaneous behavioral seizures in 82% of kainic-acid-treated mice. Irregular estrous cycles developed within 2 months after kainic acid injection. Sixty-seven percent of KA-treated mice showed disrupted estrous cycles, typically characterized by increased estrous cycle length, increased time spent in diestrus (nonfertile stage), and decreased time spent in estrus by 42 days post-KA injection. The estrous cycle disruption, however, was not accompanied by major changes in ovarian morphology or follicular development. KA-treated mice also displayed increased weight gain compared to control mice. Significance:These data indicate that comorbid female irregular estrous cyclicity arises in the intrahippocampal kainic acid mouse model of TLE. This is the first demonstration of disrupted reproductive endocrine function in a mouse model of TLE initially produced by an insult specifically targeted to the hippocampus. This model should thus be useful for basic studies investigating the neural mechanisms driving comorbid reproductive dysfunction in epilepsy in women.

Project description:ObjectivesTo investigate whether quantitative T2 mapping is complementary to [18F]FDG PET in epileptogenic zone detection, thus improving the lateralization accuracy for drug-resistant mesial temporal lobe epilepsy (MTLE) using hybrid PET/MR.MethodsWe acquired routine structural MRI, T2-weighted FLAIR, whole brain T2 mapping, and [18F]FDG PET in 46 MTLE patients and healthy controls on a hybrid PET/MR scanner, followed with computing voxel-based z-score maps of patients in reference to healthy controls. Asymmetry indexes of the hippocampus were calculated for each imaging modality, which then enter logistic regression models as univariate or multivariate for lateralization. Stereoelectroencephalography (SEEG) recordings and clinical decisions were collected as gold standard.ResultsRoutine structural MRI and T2w-FLAIR lateralized 47.8% (22/46) of MTLE patients, and FDG PET lateralized 84.8% (39/46). T2 mapping combined with [18F]FDG PET improved the lateralization accuracy by correctly lateralizing 95.6% (44/46) of MTLE patients. The asymmetry indexes of hippocampal T2 relaxometry and PET exhibit complementary tendency in detecting individual laterality, especially for MR-negative patients. In the quantitative analysis of z-score maps, the ipsilateral hippocampus had significantly lower SUVR (LTLE, p < 0.001; RTLE, p < 0.001) and higher T2 value (LTLE, p < 0.001; RTLE, p = 0.001) compared to the contralateral hippocampus. In logistic regression models, PET/T2 combination resulted in the highest AUC of 0.943 in predicting lateralization for MR-negative patients, followed by PET (AUC = 0.857) and T2 (AUC = 0.843).ConclusionsThe combination of quantitative T2 mapping and [18F]FDG PET could improve lateralization for temporal lobe epilepsy.Key points• Quantitative T2 mapping and18F-FDG PET are complementary in the characterization of hippocampal alterations of MR-negative temporal lobe epilepsy patients. • The combination of quantitative T2 and18F-FDG PET obtained from hybrid PET/MR could improve lateralization for temporal lobe epilepsy.

Project description:ObjectiveIn order to better investigate the cause/effect relationships of human mesial temporal lobe epilepsy (mTLE), we hereby describe a new non-human primate model of mTLE.MethodsTen macaques were studied and divided into 2 groups: saline control group (n?=?4) and kainic acid (KA) injection group (n?=?6). All macaques were implanted bilaterally with subdural electrodes over temporal cortex and depth electrodes in CA3 hippocampal region. KA was stereotaxically injected into the right hippocampus of macaques. All animals were monitored by video and electrocorticography (ECoG) to assess status epilepticus (SE) and subsequent spontaneous recurrent seizures (SRS). Additionally, in order to evaluate brain injury produced by SE or SRS, we used both neuroimaging, including magnetic resonance image (MRI) & magnetic resonance spectroscopy (MRS), and histological pathology, including Nissl stainning and glial fibrillary acid protein (GFAP) immunostaining.ResultsThe typical seizures were observed in the KA-injected animal model. Hippocampal sclerosis could be found by MRI & MRS. Hematoxylin and eosin (H&E) staining and GFAP immunostaining showed neuronal loss, proliferation of glial cells, formation of glial scars, and hippocampal atrophy. Electron microscopic analysis of hippocampal tissues revealed neuronal pyknosis, partial ribosome depolymerization, an abnormal reduction in rough endoplasmic reticulum size, expansion of Golgi vesicles and swollen star-shaped cells. Furthermore, we reported that KA was able to induce SE followed by SRS after a variable period of time. Similar to human mTLE, brain damage is confined to the hippocampus. Accordingly, hippocampal volume is in positive correlations with the neuronal cells count in the CA3, especially the ratio of neuron/glial cell.ConclusionsThe results suggest that a model of mTLE can be developed in macaques by intra-hippocampal injection of KA. Brain damage is confined to the hippocampus which is similar to the human mTLE. The hippocampal volume correlates with the extension of the hippocampal damage.

Project description:PurposeEpilepsy is one of the most disabling neurological disorders, which affects all age groups and often results in severe consequences. Since misdiagnoses are common, many pediatric patients fail to receive the correct treatment. Recently, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging has been used for the evaluation of pediatric epilepsy. However, the epileptic focus is very difficult to be identified by visual assessment since it may present either hypo- or hyper-metabolic abnormality with unclear boundary. This study aimed to develop a novel symmetricity-driven deep learning framework of PET imaging for the identification of epileptic foci in pediatric patients with temporal lobe epilepsy (TLE).MethodsWe retrospectively included 201 pediatric patients with TLE and 24 age-matched controls who underwent 18F-FDG PET-CT studies. 18F-FDG PET images were quantitatively investigated using 386 symmetricity features, and a pair-of-cube (PoC)-based Siamese convolutional neural network (CNN) was proposed for precise localization of epileptic focus, and then metabolic abnormality level of the predicted focus was calculated automatically by asymmetric index (AI). Performances of the proposed framework were compared with visual assessment, statistical parametric mapping (SPM) software, and Jensen-Shannon divergence-based logistic regression (JS-LR) analysis.ResultsThe proposed deep learning framework could detect the epileptic foci accurately with the dice coefficient of 0.51, which was significantly higher than that of SPM (0.24, P < 0.01) and significantly (or marginally) higher than that of visual assessment (0.31-0.44, P = 0.005-0.27). The area under the curve (AUC) of the PoC classification was higher than that of the JS-LR (0.93 vs. 0.72). The metabolic level detection accuracy of the proposed method was significantly higher than that of visual assessment blinded or unblinded to clinical information (90% vs. 56% or 68%, P < 0.01).ConclusionThe proposed deep learning framework for 18F-FDG PET imaging could identify epileptic foci accurately and efficiently, which might be applied as a computer-assisted approach for the future diagnosis of epilepsy patients.Trial registrationNCT04169581. Registered November 13, 2019 Public site: https://clinicaltrials.gov/ct2/show/NCT04169581.

Dataset Information

Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

Publications

Exploring with [<sup>18</sup>F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

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