Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [18F]FDG PET Neuroimaging
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 in...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/111261 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/111261 |
| Access Level: | acceso abierto |
| Palabra clave: | 612.8 615.01/.03 4-aminopyridine (4-AP) seizures 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) hypometabolism statistical parametric mapping (SPM) hippocampus cerebellum Diagnóstico por imagen y medicina nuclear Neurociencias (Medicina) Farmacología (Farmacia) 2490 Neurociencias 3209.10 Radiofármacos 3207.11 Neuropatología |
| Sumario: | 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. |
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