Gómez Oliver, FranciscaFernández de La Rosa, RubénBrackhan, MirjamBascuñana, PabloPozo García, Miguel ÁngelGarcía García, Luis2024-12-022024-12-022024-11-28Gómez-Oliver, F., Fernández de la Rosa, R., Brackhan, M., Bascuñana, P., Pozo, M. Á., & García-García, L. (2024). Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [18F]FDG PET Neuroimaging. International Journal of Molecular Sciences, 25(23), 12774. https://doi.org/10.3390/ijms2523127741422-006710.3390/ijms252312774https://hdl.handle.net/20.500.14352/1112614-aminopyridine (4-AP) is a non-selective blocker of voltage-dependent K+ channels used to improve walking in multiple sclerosis patients, and it may be useful in the treatment of cerebellar diseases. In animal models, 4-AP is used as a convulsant agent. When administered intrahippocampally, 4-AP induces acute local glucose hypermetabolism and significant brain damage, while i.p. administration causes less neuronal damage. This study aimed to investigate the effects of a single i.p. administration of 4-AP on acute brain glucose metabolism as well as on neuronal viability and signs of neuroinflammation 3 days after the insult. Brain glucose metabolism was evaluated by [18F]FDG PET neuroimaging. [18F]FDG uptake was analyzed based on volumes of interest (VOIs) as well as by voxel-based (SPM) analyses. The results showed that independently of the type of data analysis used (VOIs or SPM), 4-AP induced acute generalized brain glucose hypometabolism, except in the cerebellum. Furthermore, the SPM analysis normalized by the whole brain uptake revealed a significant cerebellar hypermetabolism. The neurohistochemical assays showed that 4-AP induced hippocampal astrocyte reactivity 3 days after the insult, without inducing changes in neuronal integrity or microglia-mediated neuroinflammation. Thus, acute brain glucose metabolic and neuroinflammatory profiles in response to i.p. 4-AP clearly differed from that reported for intrahippocampal administration. Finally, the results suggest that the cerebellum might be more resilient to the 4-AP-induced hypometabolism.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.3390/ijms252312774https://www.mdpi.com/1422-0067/25/23/12774open access612.8615.01/.034-aminopyridine (4-AP)seizures2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG)positron emission tomography (PET)hypometabolismstatistical parametric mapping (SPM)hippocampuscerebellumDiagnóstico por imagen y medicina nuclearNeurociencias (Medicina)Farmacología (Farmacia)2490 Neurociencias3209.10 Radiofármacos3207.11 Neuropatología