title: [(18)F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain.|Preclinical Molecular Imaging Unit, Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bascuñana
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain.|School of Psychology, Antonio Nariño University, Bogotá, Colombia.
authors.forename: Julián
authors.initials: J
authors.lastname: Javela
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain.|Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández de la Rosa
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain.
authors.forename: Ahmed Anis
authors.initials: AA
authors.lastname: Shiha
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain. lgarciag@ucm.es.|Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain. lgarciag@ucm.es.
authors.forename: Luis
authors.initials: L
authors.lastname: García-García
authors.affiliation: Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, Paseo Juan XXIII no. 1, 28040, Madrid, Spain.|Instituto Tecnológico PET, C/Manuel Bartolomé Cossío, 10, 28040, Madrid, Spain.|Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Pozo
mesh_terms: D000818:Animals; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D007696:Kindling, Neurologic / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging / Q000379:methods*; D010433:Pentylenetetrazole; D049268:Positron-Emission Tomography / Q000379:methods*; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D019788:Fluorodeoxyglucose F18; D010433:Pentylenetetrazole
keywords: Epilepsy; Hypometabolism; Kindling; Neuroimaging; Pentylenetetrazole; Small-animal PET; [18F]FDG