Lacosamide and Levetiracetam Have No Effect on Sharp-Wave Ripple Rate

Kudlacek, Jan; Chvojka, Jan; Posusta, Antonin; Kovacova, Lubica; Hong, Seung Bong; Weiss, Shennan A.; Volna, Kamila; Marusič, Petr; Otáhal, Jakub; Jiruška, Přemysl

doi:10.3389/fneur.2017.00687

Cited by 8 publications

(4 citation statements)

References 47 publications

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“…The effects of brivaracetam on ripple HFO and fast-ripple HFO remain to be clarified clinically and preclinically. The effects of levetiracetam on ripple HFO or sleep spindle remain to be clinically clarified; however, two preclinical studies revealed that levetiracetam predominantly inhibited fast-ripple HFO compared to ripple HFO [30,31]. These electrophysiological profiles of levetiracetam demonstrated by two preclinical physiological studies suggest that levetiracetam is a possible candidate antiseizure drug with reasonable pharmacological properties, predominantly suppressing fast-ripple HFO compared to ripple HFO.…”

Section: Candidate Mechanisms Of Adverse Behavioural Effects Of Briva...mentioning

confidence: 99%

“…Preclinical studies reported that levetiracetam suppressed the frequency of fast-ripple HFO, whereas the inhibitory effects of levetiracetam on the ripple HFO were weaker compared to fast-ripple HFO [30,31]. A recent systematic review reported that switching from levetiracetam to brivaracetam could improve adverse behavioural/psychiatric reactions induced by levetiracetam [32].…”

Section: Introductionmentioning

confidence: 99%

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Brivaracetam and Levetiracetam Suppress Astroglial L-Glutamate Release through Hemichannel via Inhibition of Synaptic Vesicle Protein

Fukuyama

Okada

2022

IJMS

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To explore the pathophysiological mechanisms of antiseizure and adverse behavioural/psychiatric effects of brivaracetam and levetiracetam, in the present study, we determined the effects of brivaracetam and levetiracetam on astroglial L-glutamate release induced by artificial high-frequency oscillation (HFO) bursts using ultra-high-performance liquid chromatography. Additionally, the effects of brivaracetam and levetiracetam on protein expressions of connexin43 (Cx43) and synaptic vesicle protein 2A (SV2A) in the plasma membrane of primary cultured rat astrocytes were determined using a capillary immunoblotting system. Acutely artificial fast-ripple HFO (500 Hz) burst stimulation use-dependently increased L-glutamate release through Cx43-containing hemichannels without affecting the expression of Cx43 or SV2A in the plasma membrane, whereas acute physiological ripple HFO (200 Hz) stimulation did not affect astroglial L-glutamate release or expression of Cx43 or SV2A. Contrarily, subchronic ripple HFO and acute pathological fast-ripple HFO (500 Hz) stimulations use-dependently increased L-glutamate release through Cx43-containing hemichannels and Cx43 expression in the plasma membrane. Subchronic fast-ripple HFO-evoked stimulation produced ectopic expression of SV2A in the plasma membrane, but subchronic ripple HFO stimulation did not generate ectopic SV2A. Subchronic administration of brivaracetam and levetiracetam concentration-dependently suppressed fast-ripple HFO-induced astroglial L-glutamate release and expression of Cx43 and SV2A in the plasma membrane. In contrast, subchronic ripple HFO-evoked stimulation induced astroglial L-glutamate release, and Cx43 expression in the plasma membrane was inhibited by subchronic levetiracetam administration, but was not affected by brivaracetam. These results suggest that brivaracetam and levetiracetam inhibit epileptogenic fast-ripple HFO-induced activated astroglial transmission associated with hemichannels. In contrast, the inhibitory effect of therapeutic-relevant concentrations of levetiracetam on physiological ripple HFO-induced astroglial responses probably contributes to the adverse behavioural/psychiatric effects of levetiracetam.

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Section: Candidate Mechanisms Of Adverse Behavioural Effects Of Briva...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Brivaracetam and Levetiracetam Suppress Astroglial L-Glutamate Release through Hemichannel via Inhibition of Synaptic Vesicle Protein

Fukuyama

Okada

2022

IJMS

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“…Future studies should determine whether IEDs and FRs are indeed pathologic versions of SWRs. Current antiepileptic drugs are not known to specifically affect the frequency of SWRs, but the ketogenic diet may be able to modulate pathologic oscillations . The restoration of SWRs to a physiologic state therefore represents an excellent target for the treatment of cognitive dysfunction, one of the most important comorbidities of epilepsy …”

Section: Clinical Relevancementioning

confidence: 99%

Ripple‐related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice

et al. 2019

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Summary Objective Temporal lobe epilepsy (TLE) is often associated with memory deficits. Reactivation of memory traces in the hippocampus occurs during sharp‐wave ripples (SWRs; 140‐250 Hz). To better understand the mechanisms underlying high‐frequency oscillations and cognitive comorbidities in epilepsy, we evaluated how rigorously identified deep CA1 pyramidal cells (dPCs) discharge during SWRs in control and TLE mice. Methods We used the unilateral intraamygdala kainate model of TLE in video–electroencephalography (EEG) verified chronically epileptic adult mice. Local field potential and single‐cell recordings were performed using juxtacellular recordings from awake control and TLE mice resting on a spherical treadmill, followed by post hoc identification of the recorded cells. Results Hippocampal SWRs in TLE mice occurred with increased intraripple frequency compared to control mice. The frequency of SWR events was decreased, whereas the overall frequency of SWRs, interictal epileptiform discharges, and high‐frequency ripples (250‐500 Hz) together was not altered. CA1 dPCs in TLE mice showed significantly increased firing during ripples as well as between the ripple events. The strength of ripple modulation of dPC discharges increased in TLE without alteration of the preferred phase of firing during the ripple waves. Significance These juxtacellular electrophysiology data obtained from identified CA1 dPCs from chronically epileptic mice are in general agreement with recent findings indicating distortion of normal firing patterns during offline SWRs as a mechanism underlying deficits in memory consolidation in epilepsy. Because the primary seizure focus in our experiments was in the amygdala and we recorded from the CA1 region, these results are also in agreement with the presence of altered high‐frequency oscillations in areas of secondary seizure spread.

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“…Particularly in humans, the ability to discriminate between normal HFOs and pathologic ones can be challenging because they display spectral overlap. Multiple studies tried to discriminate physiologic and pathologic HFOs according to their spectral and spatial features, relationship with sleep phases, background activity, phase relationship with slow waves, or their response to antiepileptic drugs …”

Section: In Vitro Activity With Relevance To Human Epilepsymentioning

confidence: 99%

How do we use in vitro models to understand epileptiform and ictal activity? A report of the TASK1‐WG4 group of the ILAE/AES Joint Translational Task Force

et al. 2018

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SummaryIn vitro brain tissue preparations allow the convenient and affordable study of brain networks and have allowed us to garner molecular, cellular, and electrophysiologic insights into brain function with a detail not achievable in vivo. Preparations from both rodent and human postsurgical tissue have been utilized to generate in vitro electrical activity similar to electrographic activity seen in patients with epilepsy. A great deal of knowledge about how brain networks generate various forms of epileptiform activity has been gained, but due to the multiple in vitro models and manipulations used, there is a need for a standardization across studies. Here, we describe epileptiform patterns generated using in vitro brain preparations, focusing on issues and best practices pertaining to recording, reporting, and interpretation of the electrophysiologic patterns observed. We also discuss criteria for defining in vitro seizure‐like patterns (i.e., ictal) and interictal discharges. Unifying terminologies and definitions are proposed. We suggest a set of best practices for reporting in vitro studies to favor both efficient across‐lab comparisons and translation to in vivo models and human studies.

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Lacosamide and Levetiracetam Have No Effect on Sharp-Wave Ripple Rate

Cited by 8 publications

References 47 publications

Brivaracetam and Levetiracetam Suppress Astroglial L-Glutamate Release through Hemichannel via Inhibition of Synaptic Vesicle Protein

Brivaracetam and Levetiracetam Suppress Astroglial L-Glutamate Release through Hemichannel via Inhibition of Synaptic Vesicle Protein

Ripple‐related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice

How do we use in vitro models to understand epileptiform and ictal activity? A report of the TASK1‐WG4 group of the ILAE/AES Joint Translational Task Force

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