Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy

Maxime Lévesque, Rochelle Herrington, Leila Leclerc, Michael A Rogawski, Massimo Avoli

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The objective of this study was to characterize the impact of allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80–200 Hz, fast ripples: 250–500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment with allopregnanolone (9.6–12.8 mg/kg/day) on the following day. On day 4 after SE, video-depth EEG recordings from the hippocampal CA3 subfield and the entorhinal cortex were initiated and continued for 12 consecutive days. We found that 66.7% (12/18) of untreated animals exhibited seizures compared to 28.6% (2/7) of allopregnanolone-treated animals. Interictal spikes occurred less frequently in the CA3 subfield of allopregnanolone-treated rats (n = 4) than in untreated animals presenting (n = 4) or not presenting (n = 4) with spontaneous seizures (p < 0.05), and were less frequent in the entorhinal cortex compared to both untreated groups (p < 0.05). Finally, allopregnanolone-treated rats had significantly lower rates of interictal spikes with fast ripples (250–500 Hz) compared to untreated animals but only in CA3 (p < 0.05). Our findings show that allopregnanolone reduces the frequency of interictal spikes and fast ripples in CA3, a structure that plays an important role in ictogenesis and epileptogenesis. Neurosteroids may therefore influence pathological network activity leading to spontaneous seizures following pilocarpine-induced SE. Recordings after termination of allopregnanolone treatment will be however required to establish whether allopregnanolone exerts disease-modifying properties.

Original languageEnglish (US)
Pages (from-to)12-19
Number of pages8
JournalNeuropharmacology
Volume121
DOIs
StatePublished - Jul 15 2017

Fingerprint

Pregnanolone
Temporal Lobe Epilepsy
Animal Models
Pilocarpine
Status Epilepticus
Entorhinal Cortex
Seizures
Neurotransmitter Agents
GABA-A Receptors
Sprague Dawley Rats
Electroencephalography

Keywords

  • Allopregnanolone
  • High-frequency oscillations
  • Mesial temporal lobe epilepsy
  • Neurosteroids
  • Pilocarpine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy. / Lévesque, Maxime; Herrington, Rochelle; Leclerc, Leila; Rogawski, Michael A; Avoli, Massimo.

In: Neuropharmacology, Vol. 121, 15.07.2017, p. 12-19.

Research output: Contribution to journalArticle

Lévesque, Maxime ; Herrington, Rochelle ; Leclerc, Leila ; Rogawski, Michael A ; Avoli, Massimo. / Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy. In: Neuropharmacology. 2017 ; Vol. 121. pp. 12-19.
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