Abstract：
:Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated in the pathogenesis of epilepsy and consequently as targets for anticonvulsant drugs. Consistent with this, broad-spectrum block of HCN-mediated current (Ih) reduces seizure susceptibility in a variety of epilepsy models. However, HCN channel isoforms have distinct biophysical characteristics and anatomical expression suggesting that they may play different roles in setting neuronal excitability. Here we confirm that the broad-spectrum blocker ivabradine is effective at reducing seizure susceptibility in the s.c.PTZ seizure assay and extend this, showing efficacy of this drug in a thermogenic assay that models febrile seizures. Ivabradine is also effective at reducing thermogenic seizures in the Scn1a mouse model of Dravet syndrome in which febrile seizures are a feature. HCN isoform-preferring drugs were tested in the s.c.PTZ seizure assay. We confirm that the HCN4-preferring drug, EC18, is efficacious in reducing seizure susceptibility. Conversely, the HCN2/1-preferring drug, MEL55A, increased seizure susceptibility in the s.c.PTZ seizure assay. MEL57A, an HCN1-preferring drug, had no effect on seizure susceptibility. Mouse pharmacokinetic studies (for MEL55A and MEL57A) and screening against additional ion channels have not been thoroughly investigated on the HCN isoform-preferring compounds. Our results need to be considered in this light. Nevertheless, these data suggest that HCN isoform-selective block can have a differential impact on seizure susceptibility. This motivates the need to develop more HCN isoform-selective compounds to better explore this idea.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Kharouf Q,Pinares-Garcia P,Romanelli MN,Reid CAdoi
10.1016/j.eplepsyres.2020.106484subject
Has Abstractpub_date
2020-12-01 00:00:00pages
106484eissn
0920-1211issn
1872-6844pii
S0920-1211(20)30535-0journal_volume
168pub_type
杂志文章abstract：:We have reported long-term clinical follow-up for two siblings with Lafora disease, a brother and sister, one of whom autopsied. Both siblings had repeated attacks of severe myoclonus, tonic and tonic-clonic convulsions, and intractable status epilepticus. The addition of orally administered zonisamide brought about s...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(01)00282-0
更新日期：2001-09-01 00:00:00
abstract：PURPOSE:Caffeine is a non-selective antagonist of A1 and A2A adenosine receptors (ARs). In this regard, nitric oxide (NO) is partly involved in the central effects of caffeine. In this study, we examined the effect of acute caffeine administration on pentylenetetrazole (PTZ)-induced seizure threshold by focusing on A1R...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2018.10.013
更新日期：2019-01-01 00:00:00
abstract：:Uncomplicated childhood-onset epilepsy is associated with increased brain amyloid load at late middle age, but its possible association with Alzheimer-type neurodegenerative processes is unclear. After 50-year follow-up, 42 childhood onset epilepsy subjects and 45 matched controls were investigated with [18F]fluorodeo...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2017.09.006
更新日期：2017-11-01 00:00:00
abstract：PURPOSE:Epilepsy is a diverse neurological condition with extreme genetic and phenotypic heterogeneity. The introduction of next-generation sequencing into the clinical laboratory has made it possible to investigate hundreds of associated genes simultaneously for a patient, even in the absence of a clearly defined synd...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2018.05.004
更新日期：2018-08-01 00:00:00
abstract：:Alterations in the level of consciousness may render the interpretation of the memory test results from the intracarotid amobarbital procedure difficult. The present study was designed to investigate the impact of inattention and somnolence on memory performance during the Amytal test. Nineteen consecutive patients un...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(92)90079-9
更新日期：1992-09-01 00:00:00
abstract：PURPOSE:We performed a retrospective study to investigate seizure, EEG, social and cognitive outcome in adult LGS subjects. METHODS:We retrospectively evaluated 27 LGS patients aged 40-59 years. We assessed in particular the evolution of different seizure types and EEG findings, as well as cognitive and social outcome...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2010.01.012
更新日期：2010-05-01 00:00:00
abstract：:Simultaneous electroencephalography-transcranial magnetic stimulation (EEG-TMS) investigates cortical reactivity to external perturbations. TMS evoked potentials (TEPs) have been described in normals during sleep and wake but not after sleep deprivation or in pathologically enhanced excitability, i.e., epilepsy. The a...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.05.015
更新日期：2011-09-01 00:00:00
abstract：PURPOSE:To identify clinical risk factors for Dravet syndrome (DS) in a population of children with status epilepticus (SE). MATERIAL AND METHODS:Children aged between 1 month and 16 years with at least one episode of SE were referred from 6 pediatric neurology centers in Switzerland. SE was defined as a clinical seiz...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2014.02.019
更新日期：2014-05-01 00:00:00
abstract：:We describe the clinical and radiological features of a family with a homozygous mutation in TBC1D24. The phenotype comprised onset of focal seizures at 2 months with prominent eye-blinking, facial and limb jerking with an oral sensory aura. These were controllable with medication but persisted into adult life. Associ...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2013.02.005
更新日期：2013-07-01 00:00:00
abstract：PURPOSE:Cryptogenic focal epilepsy (CFE) is a heterogeneous clinical disorder including patients with severe refractory forms and patients with a fairly good prognosis. Predictors of prognosis in CFE are poorly understood. The aim of this retrospective study is to identify long-term (5-year) prognostic predictors in pa...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2013.07.004
更新日期：2013-11-01 00:00:00
abstract：:With the availability of more stable radiopharmaceuticals, the ictal single photon emission computed tomography (SPECT) perfusion study has emerged as a useful noninvasive functional neuroimaging tool in the presurgical evaluation of patients with medically intractable partial epilepsy. The purpose of this study was t...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(98)00097-7
更新日期：1999-02-01 00:00:00
abstract：:Special issues are related to AED testing in several populations. Pharmacokinetics, pharmacodynamics and underlying neurochemistry and developing systems require specific testing in appropriate infants with refractory seizures. EEG monitoring is an essential part of seizure definition and recognition, making it a nece...
journal_title：Epilepsy research
pub_type： 杂志文章,评审
doi：10.1016/j.eplepsyres.2005.09.017
更新日期：2006-01-01 00:00:00
abstract：:Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Daw...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2015.09.009
更新日期：2015-11-01 00:00:00
abstract：:Interpreting electrocorticography (ECoG) in the context of neuroimaging requires that multimodal information be integrated accurately. However, the implantation of ECoG electrodes can shift the brain impacting the spatial interpretation of electrode locations in the context of pre-implant imaging. We characterized the...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2020.106410
更新日期：2020-11-01 00:00:00
abstract：PURPOSE:We investigated long term prognosis of Lennox-Gastaut syndrome (LGS) with active application of recent advanced treatment modalities such as ketogenic diet (KD) or epilepsy surgery (ES). METHODS:We retrospectively evaluated 68 patients with LGS, aged 18-35 years. We assessed seizure outcomes for a range of the...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2014.11.004
更新日期：2015-02-01 00:00:00
abstract：:Although memory, language, and executive functions have been extensively studied in patients with mesial temporal lobe epilepsy (MTLE), few investigations of the decision-making abilities of these patients have been performed. We studied implicit decision-making (decisions under ambiguity) in right and left MTLE patie...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2010.10.009
更新日期：2011-01-01 00:00:00
abstract：:The effect and safety of loreclezole were evaluated during a long-term follow-up trial targeting higher plasma concentrations than those of the preceding controlled trial. The result is better than in the double-blind trial, in which loreclezole doses were administered to reach plasma concentrations of 1-2 mg/l and 6/...
journal_title：Epilepsy research
pub_type： 临床试验,杂志文章
doi：10.1016/0920-1211(91)90048-k
更新日期：1991-05-01 00:00:00
abstract：:In control rats, we examined the effects of ketogenic diet on NKCC1 and KCC2 expression levels in hippocampus. Neither the number of NKCC1 immunoreactive cells nor the intensity of labeling of KCC2 was found to modify in hippocampus of the rats after ketogenic diet treatment. These results indicate that ketogenic diet...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.05.017
更新日期：2011-09-01 00:00:00
abstract：:In this preliminary study, we evaluated the predictive ability of Correlation Dimension (CD) and Nonlinear Interdependence (NI) for seizures in pediatric myoclonic epilepsy patients. Scalp EEG recordings of eight diagnosed cases of myoclonic epilepsy were analyzed using Receiver Operating Curve (ROC) for discriminatin...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2017.06.011
更新日期：2017-09-01 00:00:00
abstract：:Dapsone (4,4'-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(91)90001-v
更新日期：1991-11-01 00:00:00
abstract：:Clinical and epidemiological studies have repeatedly demonstrated that a subset of patients with epilepsy have progressive syndromes with increasing seizure frequency and cumulative adverse effects despite optimal anticonvulsant therapy. Recent longitudinal imaging studies and long-term neuropsychological studies have...
journal_title：Epilepsy research
pub_type： 杂志文章,评审
doi：10.1016/j.eplepsyres.2004.07.001
更新日期：2004-07-01 00:00:00
abstract：:In rats with electrodes implanted in the hippocampus or amygdala, the effect was studied of a single episode of low frequency stimulation (125 msec, biphasic 4 Hz, for 1 min at a current 50% of threshold for after-discharge), LFS, on the after-discharge thresholds (ADTs) during the course of hippocampal and amygdaloid...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(89)90029-6
更新日期：1989-05-01 00:00:00
abstract：INTRODUCTION:Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. METHODS:We retrospectively studied 242 patients with JME at the Department of Neurology, Me...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2014.09.008
更新日期：2014-12-01 00:00:00
abstract：:Interactions of subclinical epileptiform EEG discharges and cognitive functioning were studied in 91 patients with epilepsy, under video monitoring, to exclude overt clinical ictal phenomena during the investigations. A short-term memory test was presented as an engaging television game, in two versions, using spatial...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/0920-1211(87)90031-3
更新日期：1987-07-01 00:00:00
abstract：:Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved recently in Europe as adjunctive therapy for refractory partial seizures in adults, has been used extensively in Japan and the United States. A substantial body of clinical experience has accumulated over a 14-year period, allowing the properties and pha...
journal_title：Epilepsy research
pub_type： 杂志文章,评审
doi：10.1016/j.eplepsyres.2005.11.004
更新日期：2006-02-01 00:00:00
abstract：:The present study examined the relationship between the patterns and densities of glutamate AMPA receptor sub-units GluR1 and GluR2/3 in the molecular layer of the fascia dentata and aberrant mossy fiber neoinnervation in human and kainate rat hippocampal epilepsy. Because AMPA sub-units modulate the fast glutamate sy...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/s0920-1211(96)00053-8
更新日期：1996-12-01 00:00:00
abstract：OBJECTIVE:We performed targeted gene-panel sequencing for children with developmental and epileptic encephalopathy (DEE) and evaluated the clinical implications of genotype-phenotype correlations. METHODS:We assessed 278 children with DEE using a customized gene panel that included 172 genes, and extensively reviewed ...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2018.02.003
更新日期：2018-03-01 00:00:00
abstract：PURPOSE:The present study aims to determine the initialization and propagation of typical absence seizures using magnetoencephalography (MEG). METHOD:Fourteen drug-naïve children with childhood absence epilepsy (CAE) were studied using a 275-Channel MEG system. The spectral signatures of epileptic activity were assess...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2014.01.006
更新日期：2014-03-01 00:00:00
abstract：OBJECTIVE:To determine the relative bioavailability and tolerability of a topiramate (TPM) suspension after rectal administration. DESIGN/METHOD:Seven healthy men and five healthy non-pregnant women were enrolled. A 100 or 200 mg tablet of TPM was given orally and a 200 mg dose was given rectally in a randomized, open...
journal_title：Epilepsy research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s0920-1211(03)00083-4
更新日期：2003-05-01 00:00:00
abstract：INTRODUCTION:The aim of this study was to determine the histological effects of valproic acid (VPA) on the penis in prepubertal rats. METHODS:Twelve male Wistar rats (21-24 days old) were divided equally into 2 experimental groups, and given tap water (control group) or 300mg/kg/day VPA via gavage for 30 days. After t...
journal_title：Epilepsy research
pub_type： 杂志文章
doi：10.1016/j.eplepsyres.2011.12.010
更新日期：2012-05-01 00:00:00
