Pablo Bascuñana1,2, Julián Javela1,3, Mercedes Delgado1,4, Rubén Fernández de la Rosa1, Ahmed Anis Shiha1, Luis García-García5,6, Miguel Ángel Pozo1,7,8. 1. Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain. 2. Preclinical Molecular Imaging Unit, Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany. 3. School of Psychology, Antonio Nariño University, Bogotá, Colombia. 4. Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain. 5. Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain. lgarciag@ucm.es. 6. Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain. lgarciag@ucm.es. 7. Instituto Tecnológico PET, C/Manuel Bartolomé Cossío, 10, 28040, Madrid, Spain. 8. Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain.
Abstract
PURPOSE: Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter. PROCEDURES: In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism. RESULTS: The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [(18)F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session. CONCLUSION: Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.
PURPOSE: Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter. PROCEDURES: In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism. RESULTS: The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [(18)F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session. CONCLUSION: Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.
Authors: Terence J O'Brien; Ken Miles; Robert Ware; Mark J Cook; David S Binns; Rodney J Hicks Journal: J Nucl Med Date: 2008-05-15 Impact factor: 10.057
Authors: B P Keogh; D Cordes; L Stanberry; B D Figler; C A Robbins; B L Tempel; C G Green; A Emmi; K M Maravilla; P A Schwartzkroin Journal: Epilepsy Res Date: 2005 Aug-Sep Impact factor: 3.045
Authors: N Foldvary; N Lee; M W Hanson; R E Coleman; C M Hulette; A H Friedman; M D Bej; R A Radtke Journal: Epilepsia Date: 1999-01 Impact factor: 5.864
Authors: J Delforge; S Pappata; P Millet; Y Samson; B Bendriem; A Jobert; C Crouzel; A Syrota Journal: J Cereb Blood Flow Metab Date: 1995-03 Impact factor: 6.200
Authors: Ga Young Park; Eun Mi Lee; Min-Soo Seo; Yoo-Jin Seo; Jungsu S Oh; Woo-Chan Son; Ki Soo Kim; Jae Seung Kim; Joong Koo Kang; Kyung-Sun Kang Journal: J Korean Med Sci Date: 2015-08-13 Impact factor: 2.153
Authors: Pablo Bascuñana; Mirjam Brackhan; Ina Leiter; Heike Keller; Ina Jahreis; Tobias L Ross; Frank M Bengel; Marion Bankstahl; Jens P Bankstahl Journal: J Cereb Blood Flow Metab Date: 2018-10-30 Impact factor: 6.200