Neurosteroids can modulate γ-aminobutyric acid type A receptor-mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α-dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE. For this reason, first we evaluated whether the inhibitor of adrenocortical steroid production trilostane (50 mg/kg) could modify the levels of neurosteroids in the hippocampus and neocortex, and we found a remarkable increase in pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone levels using liquid chromatography tandem mass spectrometry. Second, we characterized the dynamics of SE in the presence of the varied neurosteroidal milieu by a single intraperitoneal kainic acid (KA; 15 mg/kg) injection in trilostane-treated rats and their controls. Convulsions started in advance in the trilostane group, already appearing 90 minutes after the KA injection. In contrast to controls, convulsions prevalently developed as generalized seizures with loss of posture in the trilostane group. However, this effect was transient, and convulsions waned 2 hours before the control group. Moreover, electrocorticographic traces of convulsions were shorter in trilostane-treated rats, especially at the 180-minute (P < .001) and 210-minute (P < .01) time points. These findings indicate that endogenous neurosteroids remarkably modulate SE dynamics.

Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics / Lucchi, C.; Costa, A. M.; Senn, L.; Messina, S.; Rustichelli, C.; Biagini, G.. - In: EPILEPSIA. - ISSN 1528-1167. - 61:9(2020), pp. e129-e134. [10.1111/EPI.16654]

Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics

Lucchi C.;Costa A. M.;Senn L.;Rustichelli C.;Biagini G.
2020

Abstract

Neurosteroids can modulate γ-aminobutyric acid type A receptor-mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α-dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE. For this reason, first we evaluated whether the inhibitor of adrenocortical steroid production trilostane (50 mg/kg) could modify the levels of neurosteroids in the hippocampus and neocortex, and we found a remarkable increase in pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone levels using liquid chromatography tandem mass spectrometry. Second, we characterized the dynamics of SE in the presence of the varied neurosteroidal milieu by a single intraperitoneal kainic acid (KA; 15 mg/kg) injection in trilostane-treated rats and their controls. Convulsions started in advance in the trilostane group, already appearing 90 minutes after the KA injection. In contrast to controls, convulsions prevalently developed as generalized seizures with loss of posture in the trilostane group. However, this effect was transient, and convulsions waned 2 hours before the control group. Moreover, electrocorticographic traces of convulsions were shorter in trilostane-treated rats, especially at the 180-minute (P < .001) and 210-minute (P < .01) time points. These findings indicate that endogenous neurosteroids remarkably modulate SE dynamics.
14-set-2020
61
9
e129
e134
Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics / Lucchi, C.; Costa, A. M.; Senn, L.; Messina, S.; Rustichelli, C.; Biagini, G.. - In: EPILEPSIA. - ISSN 1528-1167. - 61:9(2020), pp. e129-e134. [10.1111/EPI.16654]
Lucchi, C.; Costa, A. M.; Senn, L.; Messina, S.; Rustichelli, C.; Biagini, G.
File in questo prodotto:
File Dimensione Formato  
epi16654-sup-0001-supinfo (1).docx

accesso aperto

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 584.84 kB
Formato Microsoft Word XML
584.84 kB Microsoft Word XML Visualizza/Apri
Epilepsia Trilostane.pdf

embargo fino al 14/10/2020

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 545.36 kB
Formato Adobe PDF
545.36 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1209935
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact