Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [ 18 F]FDG PET Neuroimaging

• Published in: International journal of molecular sciences 2024-12, Vol.25 (23), p.12774
• Main Authors: Gómez-Oliver, Francisca, Fernández de la Rosa, Rubén, Brackhan, Mirjam, Bascuñana, Pablo, Pozo, Miguel Ángel, García-García, Luis
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; Animals; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain damage; Convulsions & seizures; Epilepsy; Fluorodeoxyglucose F18; Glucose; Glucose - metabolism; Male; Medical imaging; Metabolism; Multiple sclerosis; Musculoskeletal system; Neurodegeneration; Neuroimaging; Neuroimaging - methods; Positron-Emission Tomography - methods; Rats; Rats, Wistar; Seizures - chemically induced; Seizures - diagnostic imaging; Seizures - drug therapy; Seizures - metabolism
• ISSN: 1661-6596; 1422-0067
• DOI: 10.3390/ijms252312774

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 [ F]FDG PET neuroimaging. [ F]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.