Neurosteroids modulate epileptiform activity and associated high-frequency oscillations in the piriform cortex

Herrington, Rochelle; Lévesque, Maxime

doi:10.1016/j.neuroscience.2013.10.025

Cited by 11 publications

(12 citation statements)

References 47 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have confirmed here that ionotropic glutamatergic receptor-mediated signaling is required for the generation of ictal discharges in both PC and EC (Avoli et al, 2013;Hamidi et al, 2014;Herrington et al, 2014). In keeping with evidence obtained in these previous studies, we have found that blockade of glutamatergic signaling using NMDA and non-NMDA receptor antagonists led to the occurrence of isolated, slow GABA receptordependent potentials during application of 4AP.…”

Section: Modulation Of Isolated Gabaergic Events By Kcc2 Blockers Andsupporting

confidence: 91%

KCC2 function modulates in vitro ictogenesis

Hamidi

Avoli

2015

Neurobiology of Disease

View full text Add to dashboard Cite

GABA A receptor-mediated inhibition is active and may contribute to epileptiform synchronization. The efficacy of inhibition relies on low levels of intracellular Cl − , which are controlled by KCC2 activity. This evidence has led us to analyze with field potential recordings the effects induced by the KCC2 blockers VU0240551 (10 μM) or bumetanide (50 μM) and by the KCC2 enhancer CLP257 (100 μM) on the epileptiform discharges generated by piriform and entorhinal cortices (PC and EC, respectively) in an in vitro brain slice preparation. Ictal-and interictal-like discharges along with high-frequency oscillations (HFOs, ripples: 80-200 Hz, fast ripples: 250-500 Hz) were recorded from these two regions during application of 4-aminopyridine (4AP, 50 μM). Blocking KCC2 activity with either VU024055 or high doses of bumetanide abolished ictal discharge in both PC and EC; in addition, these experimental procedures decreased the interval of occurrence and duration of interictal discharges. In contrast, enhancing KCC2 activity with CLP257 increased ictal discharge duration in both regions. Finally, blocking KCC2 activity decreased the duration and amplitude of pharmacologically isolated synchronous GABAergic events whereas enhancing KCC2 activity led to an increase in their duration. Our data demonstrate that in vitro ictogenesis is abolished or facilitated by inhibiting or enhancing KCC2 activity, respectively. We propose that these effects may result from the reduction of GABA A receptor-dependent increases in extracellular K + that are known to rest on KCC2 function.

show abstract

Section: Modulation Of Isolated Gabaergic Events By Kcc2 Blockers Andsupporting

confidence: 91%

KCC2 function modulates in vitro ictogenesis

Hamidi

Avoli

2015

Neurobiology of Disease

View full text Add to dashboard Cite

show abstract

“…As previously shown by our group, THDOC administration reduced HFO occurrence in PC of control tissue (Herrington et al, 2013). We have found that in both PC and EC of epileptic tissue, adding THDOC to the bathing solution greatly increased the occurrence of ripples during interictal discharges.…”

Section: Thdoc Modulation Of Hfos In Epileptic Tissuesupporting

confidence: 83%

“…Slices were allowed to recover for 90 min before the K + channel blocker, 4AP (50 μM), was bath-applied at a rate of ~2 ml/min to induce epileptiform activity. Previous studies have shown that lower concentrations of THDOC failed to modulate 4AP-induced epileptiform activity; Therefore, we applied THDOC (5 μM) at a rate of ~2 ml/min for ~30 min (Herrington et al, 2013(Herrington et al, , 2014Salazar et al, 2003). All pharmaceutical compounds were obtained from Sigma-Aldrich Canada, Ltd. (Oakville, Ontario, Canada).…”

Section: Preparation Of Brain Slices For Electrophysiological Recordingsmentioning

confidence: 99%

“…The K + channel blocker 4AP, is a common convulsant used in vivo (Fragoso-Veloz et al, 1990;Mihály et al, 1990) and in vitro (Hamidi et al, 2014;Herrington et al, 2013;Panuccio et al, 2012) to induce epileptiform synchronization by enhancing both GABAergic and glutamatergic neurotransmission (Perreault and Avoli, 1991;Rutecki et al, 1987). It has been reported that brain slices obtained from epileptic rats are characterized by a reduced ability to generate ictal discharges in vitro during 4AP treatment when recordings are performed in the medial EC (Zahn et al, 2012).…”

Section: Ap-induced Epileptiform Discharges In Control and Epilepticmentioning

confidence: 99%

“…Our group has previously characterized 4AP-induced epileptiform discharges in PC and EC (Hamidi et al, 2014) and has reported the effects of neurosteroids on such epilepti-form activity and HFOs in the PC of healthy rats (Herrington et al, 2013). It remains however unknown whether these effects are maintained in the epileptic brain.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neurosteroidal modulation of in vitro epileptiform activity is enhanced in pilocarpine-treated epileptic rats

Shiri

Herrington

Lévesque

2015

Neurobiology of Disease

View full text Add to dashboard Cite

We employed field potential recordings in brain slices obtained from pilocarpine-treated epileptic (4-5 weeks following a pilocarpine-induced status epilepticus) and age-matched, non-epileptic control (NEC) rats to establish the effects of the neurosteroid allotetrahydrodeoxycorticosterone (THDOC) on the epileptiform activity -including high frequency oscillations (HFOs; ripples: 80-200 Hz, fast ripples: 250-500 Hz) -induced by 4-aminopyridine (4AP) in piriform (PC) and entorhinal (EC) cortices. Both structures are highly susceptible to generate seizures and may also be involved in epileptogenesis. We found that THDOC application to pilocarpine-treated slices: (i) decreased interictal discharge frequency in PC while increasing it in EC; (ii) abolished ictal discharges in both areas in approx. one third of the experiments and reduced them in frequency and duration in the remaining experiments; and (iii) increased the occurrence of ripples and fast ripples associated to interictal events, and modified their pattern of occurrence during ictal discharges in both PC and EC. These effects were either weaker or absent in NEC tissue. Our results demonstrate that THDOC plays a structure-dependent modulatory role in epileptiform synchronization in the pilocarpine-treated epileptic rat brain where its actions are more pronounced than in NEC tissue. This evidence supports the application of neurosteroids as potential antiepileptic tools.

show abstract

Limbic Networks and Epileptiform Synchronization

Behr

D’Antuono

Hamidi

et al. 2014

International Review of Neurobiology

View full text Add to dashboard Cite

In this review, we summarize findings obtained in acute and chronic epilepsy models and in particular experiments that have revealed how neuronal networks in the limbic system-which is closely involved in the pathophysiogenesis of mesial temporal lobe epilepsy (MTLE)-produce hypersynchronous discharges. MTLE is often associated with a typical pattern of brain damage known as mesial temporal sclerosis, and it is one of the most refractory forms of partial epilepsy in adults. Specifically, we will address the cellular and pharmacological features of abnormal electrographic events that, as in MTLE patients, can occur in in vivo and in vitro animal models; these include interictal and ictal discharges along with high-frequency oscillations. In addition, we will consider how different limbic structures made hyperexcitable by acute pharmacological manipulations interact during epileptiform discharge generation. We will also review the electrographic characteristics of two types of seizure onsets that are most commonly seen in human and experimental MTLE as well as in in vitro models of epileptiform synchronization. Finally, we will address the role played by neurosteroids in reducing epileptiform synchronization and in modulating epileptogenesis.

show abstract

Neurosteroids modulate epileptiform activity and associated high-frequency oscillations in the piriform cortex

Cited by 11 publications

References 47 publications

KCC2 function modulates in vitro ictogenesis

KCC2 function modulates in vitro ictogenesis

Neurosteroidal modulation of in vitro epileptiform activity is enhanced in pilocarpine-treated epileptic rats

Limbic Networks and Epileptiform Synchronization

Contact Info

Product

Resources

About