The vasodilator naftidrofuryl attenuates short-term brain glucose hypometabolism in the lithium-pilocarpine rat model of status epilepticus without providing neuroprotection

• Published in: European journal of pharmacology 2023-01, Vol.939, p.175453, Article 175453
• Main Authors: García-García, Luis, Gomez, Francisca, Delgado, Mercedes, Fernández de la Rosa, Rubén, Pozo, Miguel Ángel
• Format: Article
• Language: English
• Subjects: [18F]FDG PET; Animals; Brain; Cerebral blood flow; Disease Models, Animal; Glucose - metabolism; Glucose hypometabolism; Hippocampal damage; Hippocampus; Humans; Lithium - pharmacology; Lithium-pilocarpine model; Nafronyl - metabolism; Nafronyl - pharmacology; Neuroinflammation; Neuroprotection; Pilocarpine - pharmacology; Rats; Seizures - metabolism; Status Epilepticus - chemically induced; Status Epilepticus - diagnostic imaging; Status Epilepticus - drug therapy; Vasodilator Agents - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2022.175453

Status epilepticus (SE) triggered by lithium-pilocarpine is a model of epileptogenesis widely used in rats, reproducing many of the pathological features of human temporal lobe epilepsy (TLE). After the SE, a silent period takes place that precedes the occurrence of recurrent spontaneous seizures. This latent stage is characterized by brain glucose hypometabolism and intense neuronal damage, especially at the hippocampus. Importantly, interictal hypometabolism in humans is a predictive marker of epileptogenesis, being correlated to the extent and severity of neuronal damage. Among the potential mechanisms underpinning glucose metabolism impairment and the subsequent brain damage, a reduction of cerebral blood flow has been proposed. Accordingly, our goal was to evaluate the potential beneficial effects of naftidrofuryl (25 mg/kg i.p., twice after the insult), a vasodilator drug currently used for circulatory insufficiency-related pathologies. Thus, we measured the effects of naftidrofuryl on the short-term brain hypometabolism and hippocampal damage induced by SE in rats. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) neuroimaging along with various neurohistochemical assays aimed to assess brain damage were performed. SE led to both severe glucose hypometabolism in key epilepsy-related areas and hippocampal neuronal damage. Although naftidrofuryl showed no anticonvulsant properties, it ameliorated the short-term brain hypometabolism induced by pilocarpine. Strikingly, the latter was neither accompanied by neuroprotective nor by anti-inflammatory effects. We suggest that naftidrofuryl, by acutely enhancing brain blood flow around the time of SE improves the brain metabolic state but this effect is not enough to protect from the damage induced by SE. •SE induced by pilocarpine in rats leads to short-term brain glucose hypometabolism.•SE was associated to severe neurodegeneration and neuroinflammation.•The vasodilator naftidrofuryl attenuated brain hypometabolism induced by SE.•Naftidrofuryl showed no anticonvulsant activity in the lithium-pilocarpine model.•Naftidrofuryl had neither neuroprotective nor antiinflammatory effects.