Metyrapone prevents brain damage induced by status epilepticus in the rat lithium-pilocarpine model

Neuropharmacology
Luis García-GarcíaMiguel A Pozo

Abstract

The status epilepticus (SE) induced by lithium-pilocarpine is a well characterized rodent model of the human temporal lobe epilepsy (TLE) which is accompanied by severe brain damage. Stress and glucocorticoids markedly contribute to exacerbate neuronal damage induced by seizures but the underlying mechanisms are poorly understood. Herein we sought to investigate whether a single administration of metyrapone (150 mg/kg, i.p.), an 11β-hydroxylase inhibitor, enzyme involved in the peripheral and central synthesis of corticosteroids, had neuroprotective properties in this model. Two experiments were carried out. In exp. 1, metyrapone was administered 3 h before pilocarpine injection whereas in exp. 2, metyrapone administration took place at the onset of the SE. In both experiments, 3 days after the insult, brain metabolism was assessed by in vivo 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography (PET). Brains were processed for analyses of markers of hippocampal integrity (Nissl staining), neurodegeneration (Fluoro-Jade C), astrogliosis (glial fibrillary acidic protein (GFAP) immunohistochemistry) and, for a marker of activated microglia by in vitro autoradiography with the TSPO (18 kDa translocator protein) r...Continue Reading

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Citations

Apr 16, 2019·Frontiers in Cellular Neuroscience·Xiaolin DengXiaohong Shi
Jan 11, 2019·International Journal of Molecular Sciences·Sandesh D ReddyDoodipala Samba Reddy
Oct 18, 2019·Frontiers in Neuroscience·Elian da Silva FranciscoRubem Carlos Araújo Guedes
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Oct 31, 2020·Molecular Neurobiology·Igor Santana de MeloOlagide Wagner de Castro
Oct 16, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Shareen Singh, Thakur Gurjeet Singh

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