Seizures Triggered by Systemic Administration of 4-Aminopyridine Lead to Acute Brain Glucose Hypometabolism in Rats, as Assessed by PET Molecular Imaging

4-aminopyridine (4-AP) is a non-selective blocker of voltage-dependent K+ channels used to im-prove 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. Intrahippocampal 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. admin-istration of 4-AP on acute brain glucose metabolism and to assess the short-term effects on neu-ronal viability and signs of neuroinflammation. We evaluated 4-AP-induced acute changes in brain glucose metabolism by [18F]FDG PET neuroimaging evaluated by standard volumes of interest (VOIs) and voxel-based (SPM) analyses. We show that 4-AP induces acute generalized brain glucose hypometabolism, except in the cerebellum, area that was significantly more resilient to this effect. Accordingly, to the appropriate neurohistochemical assays, 4-AP induced hippocampal astrocyte reactivity 3 days after the insult, without changes in signs of neuronal integrity or micro-glia-mediated neuroinflammation. Thus, acute brain glucose metabolic and short-term neuroin-flammatory profiles in response to 4-AP i.p. clearly differ from that reported for intracerebral administration. Our results also suggest cerebellar metabolism as a potential marker of the effects of 4-AP.