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[<sup>18</sup>F]FDG PET Neuroimaging Pbkp_redicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats

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 unpbkp_redictability. 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 pbkp_redictive kindling outcome parameter. Procedures: In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]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 [18F]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 [18F]FDG uptake normalized to pons turned out to be a pbkp_redictive 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 [18F]FDG uptake of the hippocampus proved to be an early pbkp_redictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.