2026-07-25T16:40:34Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1100472025-08-29T17:19:48Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author García García, Luis author Gómez Oliver, Francisca author Fernández de La Rosa, Rubén author Pozo García, Miguel Ángel 2024-11-06T08:07:20Z 2024-11-06T08:07:20Z 2024 García-García, L., Gómez-Oliver, F., Fernández de la Rosa, R., & Pozo, M. Á. (2024). Dantrolene paradoxically exacerbates short-term brain glucose hypometabolism, hippocampal damage and neuroinflammation induced by status epilepticus in the rat lithium-pilocarpine model. European journal of pharmacology, 985, 177073. Advance online publication. https://doi.org/10.1016/j.ejphar.2024.177073 0014-2999 10.1016/j.ejphar.2024.177073 https://hdl.handle.net/20.500.14352/110047 1879-0712 https://doi.org/10.1016/j.ejphar.2024.177073 https://www.sciencedirect.com/science/article/pii/S0014299924007635 Status epilepticus (SE) is a neurologic emergency characterized by prolonged or rapidly recurring seizures. Increased intracellular calcium concentration ([Ca2+]i) occurring after SE is a key mediator of excitotoxicity that contributes to the brain damage associated with the development of epilepsy. Accumulated evidence indicates that dantrolene, a ryanodine receptor (RyR) blocker may have protective effects against the SE-induced damage. We evaluated whether dantrolene (10 mg/kg, i.p.) administered twice, 5 min and 24 h after the lithium-pilocarpine-induced SE in rats, had neuroprotective effects. Dantrolene by itself had no effects on control rats. However, it exacerbated the signs of damage in rats that underwent SE, increasing brain glucose hypometabolism as measured by PET neuroimaging 3 days after SE. Likewise, the neurohistochemical studies revealed that dantrolene aggravated signs of hippocampal neurodegeneration, neuronal death and microglia-induced neuroinflammation. Besides, the damaging effects were reflected by severe body weight loss. Overall, our results point towards a deleterious effect of dantrolene in the lithium-pilocarpine-induced SE model. Nonetheless, our results are in opposition to the reported neuroprotective effects of dantrolene. Whether the mechanisms underlying [Ca2+]i increase might significantly differ depending on the particularities of the model of epilepsy used and general experimental conditions need further studies. Besides, it is yet to be determined which isoform of RyRs significantly contributes to Ca2+-induced excitotoxicity in the lithium-pilocarpine SE rat model. eng Attribution-NonCommercial-NoDerivatives 4.0 International Dantrolene paradoxically exacerbates short-term brain glucose hypometabolism, hippocampal damage and neuroinflammation induced by status epilepticus in the rat lithium-pilocarpine model journal article 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