RT Journal Article
T1 Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [18F]FDG PET Neuroimaging
A1 Gómez Oliver, Francisca
A1 Fernández de La Rosa, Rubén
A1 Brackhan, Mirjam
A1 Bascuñana, Pablo
A1 Pozo García, Miguel Ángel
A1 García García, Luis
AB 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.
PB MDPI
SN 1422-0067
YR 2024
FD 2024-11-28
LK https://hdl.handle.net/20.500.14352/111261
UL https://hdl.handle.net/20.500.14352/111261
LA eng
NO Gómez-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/ijms252312774
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 9 abr 2025