Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep;61(9):e129-e134.
doi: 10.1111/epi.16654. Epub 2020 Sep 14.

Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics

Chiara Lucchi  1 , Anna Maria Costa  1 , Lara Senn  1 , Simone Messina  1 , Cecilia Rustichelli  2 , Giuseppe Biagini  1   3
Affiliations

Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics

Chiara Lucchi et al. Epilepsia. 2020 Sep.

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.

Keywords: status epilepticus; LC-MS/MS; allopregnanolone; hippocampus; kainic acid; trilostane.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Trinka E, Höfler J, Zerbs A. Causes of status epilepticus. Epilepsia. 2012;53(Suppl 4):127-38.
    1. Meletti S, Lucchi C, Monti G, Giovannini G, Bedin R, Trenti T, et al. Low levels of progesterone and derivatives in cerebrospinal fluid of patients affected by status epilepticus. J Neurochem. 2018;147:275-84.
    1. Belelli D, Lambert JJ. Neurosteroids: endogenous regulators of the GABAA receptor. Nat Rev Neurosci. 2005;6:565-75.
    1. Rosenthal ES, Claassen J, Wainwright MS, Husain AM, Vaitkevicius H, Raines S, et al. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol. 2017;82:342-52.
    1. Lemetayer J, Blois S. Update on the use of trilostane in dogs. Can Vet J. 2018;59:397-407.

Publication types

MeSH terms

LinkOut - more resources

-