{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:42Z","timestamp":1760146662695,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Spanish Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["Retos PID2019-106968RB-100"],"award-info":[{"award-number":["Retos PID2019-106968RB-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>4-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.<\/jats:p>","DOI":"10.3390\/ijms252312774","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T03:21:23Z","timestamp":1732764083000},"page":"12774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [18F]FDG PET Neuroimaging"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5896-3107","authenticated-orcid":false,"given":"Francisca","family":"G\u00f3mez-Oliver","sequence":"first","affiliation":[{"name":"Unidad de Cartograf\u00eda Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Departamento de Farmacolog\u00eda, Farmacognosia y Bot\u00e1nica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n","family":"Fern\u00e1ndez de la Rosa","sequence":"additional","affiliation":[{"name":"Unidad de Cartograf\u00eda Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Infraestructura Cient\u00edfico-T\u00e9cnica Singular Bioimagen Complutense (ICTS BIOIMAC), Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjam","family":"Brackhan","sequence":"additional","affiliation":[{"name":"Unidad de Cartograf\u00eda Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2186-8899","authenticated-orcid":false,"given":"Pablo","family":"Bascu\u00f1ana","sequence":"additional","affiliation":[{"name":"Unidad de Cartograf\u00eda Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-0513","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Pozo","sequence":"additional","affiliation":[{"name":"Unidad de Cartograf\u00eda Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"},{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-5387","authenticated-orcid":false,"given":"Luis","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Cartograf\u00eda Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Departamento de Farmacolog\u00eda, Farmacognosia y Bot\u00e1nica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1527-3458.2004.tb00029.x","article-title":"The Use of 4-Aminopyridine (Fampridine) in Demyelinating Disorders","volume":"10","author":"Hayes","year":"2004","journal-title":"CNS Drug Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0920-1211(03)00113-X","article-title":"Seizure, Neurotransmitter Release, and Gene Expression Are Closely Related in the Striatum of 4-Aminopyridine-Treated Rats","volume":"55","author":"Szente","year":"2003","journal-title":"Epilepsy Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2174\/157015906775203002","article-title":"Animal Models for the Development of New Neuropharmacological Therapeutics in the Status Epilepticus","volume":"4","author":"Martin","year":"2005","journal-title":"Curr. 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