Evidence map›Paper›PMID 25108607›Full record

ArticleBrain stimulation

Seizure suppression by high frequency optogenetic stimulation using in vitro and in vivo animal models of epilepsy.

Chia-Chu Chiang, Thomas P Ladas, Luis E Gonzalez-Reyes, Dominique M Durand

Open access · greenAbstract read
In one paragraph

Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 67 citations in OpenAlex.

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  8. On brain stimulation in epilepsy.Brain : a journal of neurology · 2025
    Review
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  15. Involvement of GABAergic Interneuron Subtypes in 4-Aminopyridine-Induced Seizure-Like Events in Mouse Entorhinal CortexThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Chia-Chu ChiangDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Thomas P LadasDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Luis E Gonzalez-ReyesDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Dominique M DurandDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: dominique.durand@case.edu.
Case Western Reserve University · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Detection and Control of EpilepsyR01NS060757 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI DURAND, DOMINIQUE M · 2008 to 2016
$2.8M
Analysis &Control of NonSynaptic Epileptiform ActivityR01NS040785 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI DURAND, DOMINIQUE M · 2001 to 2004
$913k
NCATS NIH HHS UL1 TR000439NIGMS NIH HHS T32 GM007250NINDS NIH HHS 2R01NS060757-05A1NINDS NIH HHS R01 NS040785NINDS NIH HHS R01 NS060757
6 · The paper itself

Abstract

backgroundElectrical high frequency stimulation (HFS) has been shown to suppress seizures. However, the mechanisms of seizure suppression remain unclear and techniques for blocking specific neuronal populations are required.

objectiveThe goal is to study the optical HFS protocol on seizures as well as the underlying mechanisms relevant to the HFS-mediated seizure suppression by using optogenetic methodology.

methodsThy1-ChR2 transgenic mice were used in both vivo and in vitro experiments. Optical stimulation with pulse trains at 20 and 50 Hz was applied on the focus to determine its effects on in vivo seizure activity induced by 4-AP and recorded in the bilateral and ipsilateral-temporal hippocampal CA3 regions. In vitro methodology was then used to study the mechanisms of the in vivo suppression.

resultsOptical HFS was able to generate 82.4% seizure suppression at 50 Hz with light power of 6.1 mW and 80.2% seizure suppression at 20 Hz with light power of 2.0 mW. The suppression percentage increased by increasing the light power and saturated when the power reached above-mentioned values. In vitro experimental results indicate that seizure suppression was mediated by activation of GABA receptors. Seizure suppression effect decreased with continued application but the suppression effect could be restored by intermittent stimulation.

conclusionsThis study shows that optical stimulation at high frequency targeting an excitatory opsin has potential therapeutic application for fast control of an epileptic focus. Furthermore, electrophysiological observations of extracellular and intracellular signals revealed that GABAergic neurotransmission activated by optical stimulation was responsible for the suppression.

Indexed as

Disease Models, AnimalOptogenetics4-AminopyridineAnimalsCA3 Region, HippocampalGABA AntagonistsIn Vitro TechniquesMaleMiceMice, TransgenicNeuronsPicrotoxinReceptors, GABASeizures4-AminopyridineGABA AntagonistsPicrotoxinReceptors, GABA4-APHigh frequency stimulationHippocampusOptogeneticsSeizure suppression

Identifiers

PMID25108607
PMCPMC4259846
OpenAlexW2120203719

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.