Abstract:
:GABA transporters (GATs) are an essential element of the GABAergic system, which regulate excitability in the central nervous system and are thus used as targets for anticonvulsive therapy. However, in the immature nervous system the functions of the GABAergic system and the expression profile of GATs are distinct from the adult situation, obscuring to predict how different GAT isoforms influence epileptiform activity. Therefore we analyzed the effects of subtype specific GAT inhibitors on repetitive epileptiform discharges using field potential and whole-cell patch-clamp recordings in the CA3 region of hippocampal slices of immature (postnatal days 4-7) rats. These experiments revealed that inhibition of GAT-1 with either tiagabine (30 μM) or NO-711 (10 μM) exhibited only a minor anticonvulsive effect on repetitive epileptiform discharges. Blockade of GAT-2/3 with SNAP-5114 (40 μM) had no anticonvulsive effect, but significantly prolonged the decay of spontaneous GABAergic postsynaptic currents. In contrast, the combined application of 10 μM NO-711 and 40 μM SNAP-5114 blocked epileptiform activity in 33% of all slices and reduced the occurrence of epileptiform discharges by 54% in the remaining slices. In addition, the input resistance decreased by 10.5 ± 1.0% under this condition. These results indicate that both GAT-1 and GAT-2/3 are functional in the immature hippocampus and that only the combined inhibition of GAT 1-3 is sufficient to promote a considerable anticonvulsive effect. We conclude from these results that both GAT-1 and GAT-2/3 act synergistically to regulate the excitability in the immature hippocampus.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Sharopov S,Chen R,Sun H,Kolbaev SN,Kirischuk S,Luhmann HJ,Kilb Wdoi
10.1016/j.eplepsyres.2013.11.019subject
Has Abstractpub_date
2014-02-01 00:00:00pages
182-9issue
2eissn
0920-1211issn
1872-6844pii
S0920-1211(13)00316-1journal_volume
108pub_type
杂志文章abstract::Bupropion, a unique, non-nicotine smoking cessation aid and an effective antidepressant, is well known to produce seizures following overdosing in humans. However, the experimental background for the usefulness of antiepileptic drugs in the protection against bupropion-induced convulsions has not been established yet....
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2005.01.006
更新日期:2005-03-01 00:00:00
abstract::We have surveyed the rates at which clinicians in the U.K. and Eire withdraw antiepileptic drugs (AEDs) in patients with active epilepsy. Practice differed widely and there was a lack of consensus regarding the rates employed. Inpatient reductions were 2-4 times faster than outpatient reductions. AED reductions tended...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(87)90060-x
更新日期:1987-11-01 00:00:00
abstract:OBJECTIVE:Lamotrigine (LTG) is approved for monotherapy following withdrawal from enzyme-inducing antiepileptic drugs. LTG is also frequently used in combination with sodium valproate (VPA), and withdrawal to monotherapy in this setting is also frequently desirable. Given the known pharmacokinetic interaction between t...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2003-12-01 00:00:00
abstract::Fits of audiogenic seizures in rodents are considered as a model for generalized convulsive epilepsies in humans. The laminar distribution of the H3 histamine receptor binding densities was quantified in the motor cortex of two strains of rats with genetically determined generalized epilepsies, namely KM rats with aud...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106543
更新日期:2020-12-25 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2003.08.001
更新日期:2003-09-01 00:00:00
abstract:SUMMARY:Stereotactic radiofrequency amygdalohippocampectomy (AHE) has been reintroduced as an alternative treatment of mesial temporal lobe epilepsy. The aim of this study was to describe MRI changes after stereotactic AHE and to correlate the hippocampal and amygdalar volumes reduction with the clinical seizure outcom...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章
doi:10.1016/j.eplepsyres.2008.11.013
更新日期:2009-02-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106222
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Since intracranial electrode implantation has limited spatial sampling and carries significant risk, placement has to be effective and efficient. Structural and functional imaging of several different modalities contributes to localising the seizure onset zone (SoZ) and eloquent cortex. There is a need to su...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.08.002
更新日期:2013-11-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(93)90080-q
更新日期:1993-12-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.09.011
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to investigate regional homogeneity (ReHo) in children with new-onset drug-naïve Benign Epilepsy with Centrotemporal Spikes (BECTS), chronic BECTS and healthy controls (HC) using the Regional Homogeneity (ReHo) method applied to resting state fMRI data. METHODS:Resting state fMR...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2015.06.017
更新日期:2015-10-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.10.029
更新日期:2012-03-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2017.11.019
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:This retrospective study addresses the cost-effectiveness of add-on therapy with lamotrigine in clinical practice. METHODS:Two years' observational data of 165 patients were used. Seizure frequency, adverse effects and direct medical costs were recorded for the year before and the year after the start of lam...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2005.09.007
更新日期:2005-12-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2015.04.008
更新日期:2015-08-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2016.06.001
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:To determine the minimum enrollment duration for identifying incident cases of epilepsy in administrative data. METHODS:We performed a retrospective dynamic cohort study using Ohio Medicaid data from 1992 to 2006 to identify a total of 5037 incident epilepsy cases who had at least 1 year of follow-up prior to ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.05.005
更新日期:2013-09-01 00:00:00
abstract::Status epilepticus (SE) is a common neurological and medical emergency. Despite the significant mortality associated with SE, no human data have been available regarding cardiovascular changes prior to death in patients with this condition. This study was conducted to measure hemodynamic trends in the 24 h prior to de...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(98)00031-x
更新日期:1998-08-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.09.025
更新日期:2014-12-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106450
更新日期:2020-11-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
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更新日期:2019-11-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2015.03.004
更新日期:2015-07-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(00)00120-0
更新日期:2000-08-01 00:00:00
abstract::The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequen...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.01.010
更新日期:2011-03-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2005.07.002
更新日期:2005-08-01 00:00:00
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journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2007.05.001
更新日期:2007-07-01 00:00:00
abstract::To assess the efficacy of CM40907--a new antiepileptic drug--in suppressing inter-ictal spikes, 6 patients with severe intractable epilepsy and frequent spikes in their inter-ictal EEGs were entered in a double-blind placebo-controlled trial. The results show that CM40907 is efficacious in reducing spike counts in the...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章
doi:10.1016/0920-1211(90)90046-x
更新日期:1990-04-01 00:00:00
abstract:INTRODUCTION:Proton magnetic resonance spectroscopy ((1)H MRS) has been proposed as a lateralizing method for the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). Studies have shown correlations between temporal lobe (TL) NAA and seizure frequency, and TL NAA/Cr and the durati...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2004.06.010
更新日期:2004-12-01 00:00:00
abstract::It has previously been suggested that abnormalities in cardiac repolarization (QTc lengthening and shortening) are more likely to accompany seizures with hypoxemia and may be involved in sudden unexpected death in epilepsy (SUDEP). Accordingly, we evaluated for associations between peri-ictal QTc changes and hypoxemia...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.03.016
更新日期:2014-07-01 00:00:00
abstract::Increased excitatory amino acid transmission and decreased GABAergic inhibitory responses seem to be important mechanisms in the genesis of convulsions, where reactive oxygen species (ROS) have recently been suggested to play a critical role. Therefore, administration of antioxidants may be potentially beneficial for ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2005.08.005
更新日期:2005-08-01 00:00:00