RT Journal Article
T1 The vasodilator naftidrofuryl attenuates short-term brain glucose hypometabolism in the lithium-pilocarpine rat model of status epilepticus without providing neuroprotection
A1 García García, Luis
A1 Gómez Oliver, Francisca
A1 Delgado, Mercedes
A1 Fernández de La Rosa, Rubén
A1 Pozo García, Miguel Ángel
AB 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.
PB Elsevier
SN 0014-2999
YR 2022
FD 2022-12-11
LK https://hdl.handle.net/20.500.14352/110175
UL https://hdl.handle.net/20.500.14352/110175
LA eng
NO García-García, L., Gomez, F., Delgado, M., Fernández de la Rosa, R., & Pozo, M. Á. (2023). The vasodilator naftidrofuryl attenuates short-term brain glucose hypometabolism in the lithium-pilocarpine rat model of status epilepticus without providing neuroprotection. European journal of pharmacology, 939, 175453. https://doi.org/10.1016/j.ejphar.2022.175453
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 8 abr 2025