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epilepsy mouse model

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https://www.readbyqxmd.com/read/29683209/inhibition-of-astroglial-connexin43-hemichannels-with-tat-gap19-exerts-anticonvulsant-effects-in-rodents
#1
Laura Walrave, Anouk Pierre, Giulia Albertini, Najat Aourz, Dimitri De Bundel, Ann Van Eeckhaut, Mathieu Vinken, Christian Giaume, Luc Leybaert, Ilse Smolders
Accumulating evidence shows a key function for astrocytic connexin43 (Cx43) signaling in epilepsy. However, the lack of experimental distinction between Cx43 gap junction channels (GJCs) and hemichannels (HCs) has impeded the identification of the exact contribution of either channel configurations to epilepsy. We therefore investigated whether TAT-Gap19, a Cx mimetic peptide that inhibits Cx43 HCs but not the corresponding Cx43 GJCs, influences experimentally induced seizures in rodents. Dye uptake experiments in acute hippocampal slices of mice demonstrated that astroglial Cx43 HCs open in response to the chemoconvulsant pilocarpine and this was inhibited by TAT-Gap19...
April 23, 2018: Glia
https://www.readbyqxmd.com/read/29672844/longitudinal-positron-emission-tomography-imaging-of-glial-cell-activation-in-a-mouse-model-of-mesial-temporal-lobe-epilepsy-toward-identification-of-optimal-treatment-windows
#2
Duc-Loc Nguyen, Catriona Wimberley, Charles Truillet, Benoit Jego, Fabien Caillé, Géraldine Pottier, Raphaël Boisgard, Irène Buvat, Viviane Bouilleret
OBJECTIVE: Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process...
April 19, 2018: Epilepsia
https://www.readbyqxmd.com/read/29670100/structural-basis-of-epilepsy-related-ligand-receptor-complex-lgi1-adam22
#3
Atsushi Yamagata, Yuri Miyazaki, Norihiko Yokoi, Hideki Shigematsu, Yusuke Sato, Sakurako Goto-Ito, Asami Maeda, Teppei Goto, Makoto Sanbo, Masumi Hirabayashi, Mikako Shirouzu, Yuko Fukata, Masaki Fukata, Shuya Fukai
Epilepsy is a common brain disorder throughout history. Epilepsy-related ligand-receptor complex, LGI1-ADAM22, regulates synaptic transmission and has emerged as a determinant of brain excitability, as their mutations and acquired LGI1 autoantibodies cause epileptic disorders in human. Here, we report the crystal structure of human LGI1-ADAM22 complex, revealing a 2:2 heterotetrameric assembly. The hydrophobic pocket of the C-terminal epitempin-repeat (EPTP) domain of LGI1 binds to the metalloprotease-like domain of ADAM22...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29667129/elevation-of-mmp-9-levels-promotes-epileptogenesis-after-traumatic-brain-injury
#4
Barbara Pijet, Marzena Stefaniuk, Agnieszka Kostrzewska-Ksiezyk, Photini-Effie Tsilibary, Athina Tzinia, Leszek Kaczmarek
Posttraumatic epilepsy (PTE) is a recurrent seizure disorder that often develops secondary to traumatic brain injury (TBI) that is caused by an external mechanical force. Recent evidence shows that the brain extracellular matrix plays a major role in the remodeling of neuronal connections after injury. One of the proteases that is presumably responsible for this process is matrix metalloproteinase-9 (MMP-9). The levels of MMP-9 are elevated in rodent brain tissue and human blood samples after TBI. However, no studies have described the influence of MMP-9 on the development of PTE...
April 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29659809/a-new-mouse-model-of-arx-dup24-recapitulates-the-patients-behavioural-and-fine-motor-alterations
#5
Aline Dubos, Hamid Meziane, Giovanni Iacono, Aurore Curie, Fabrice Riet, Christelle Martin, Nadège Loaëc, Marie-Christine Birling, Mohammed Selloum, Elisabeth Normand, Guillaume Pavlovic, Tania Sorg, Henk G Stunnenberg, Jamel Chelly, Yann Humeau, Gaëlle Friocourt, Yann Hérault
The Aristaless-related homeobox (ARX) transcription factor is involved in the development of GABAergic and cholinergic neurons in the forebrain. ARX mutations have been associated with a wide spectrum of neurodevelopmental disorders in humans, among which the most frequent, a 24bp duplication in the polyalanine tract 2 (c.428_451dup24), gives rise to intellectual disability, fine motor defects with or without epilepsy. To understand the functional consequences of this mutation, we generated a partially humanized mouse model carrying the c...
April 5, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29642764/distinct-effects-of-resveratrol-on-seizures-and-hyperexcitability-induced-by-nmda-and-4-aminopyridine
#6
Ya-Jean Wang, Chung-Pin Hsieh, Ming-Huan Chan, Tzu-Yi Chan, Linyi Chen, Hwei-Hisen Chen
OBJECTIVES: The antiepileptic activity of resveratrol has been revealed in various experimental models of epilepsy. The present study evaluated the effects of resveratrol on the seizures and hyperexcitable neuronal activity associated with activation of N-methyl-d-aspartic acid (NMDA) receptor and inhibition of voltage-gated potassium channels. METHODS: The effects of resveratrol on seizure thresholds, excitatory field potentials (EFPs) and action potentials induced by NMDA and 4-aminopyridine (4-AP) were monitored in mice, the mouse cortical slices and rat cortical neurons, respectively...
April 12, 2018: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29625197/a-single-subconvulsant-dose-of-domoic-acid-at-mid-gestation-does-not-cause-temporal-lobe-epilepsy-in-mice
#7
Fanny Demars, Kristen Clark, Megan S Wyeth, Emily Abrams, Paul S Buckmaster
Harmful blooms of domoic acid (DA)-producing algae are a problem in oceans worldwide. DA is a potent glutamate receptor agonist that can cause status epilepticus and in survivors, temporal lobe epilepsy. In mice, one-time low-dose in utero exposure to DA was reported to cause hippocampal damage and epileptiform activity, leading to the hypothesis that unrecognized exposure to DA from contaminated seafood in pregnant women can damage the fetal hippocampus and initiate temporal lobe epileptogenesis. However, development of epilepsy (i...
April 3, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29616753/isobolographic-additivity-among-lacosamide-lamotrigine-and-phenobarbital-in-a-mouse-tonic-clonic-seizure-model
#8
Maria W Kondrat-Wróbel, Jarogniew J Łuszczki
BACKGROUND: Epilepsy is a serious neurological disease affecting about 1% of people worldwide (65 million). Seizures are controllable with antiepileptic drugs (AEDs) in about 70% of epilepsy patients, however, there remains about 30% of patients inadequately medicated with these AEDs, who need a satisfactory control of their seizure attacks. For these patients, one of the treatment options is administration of 2 or 3 AEDs in combination. OBJECTIVES: To determine the anticonvulsant effects of a combination of 3 selected AEDs (i...
March 28, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29599705/of-men-and-mice-modeling-the-fragile-x-syndrome
#9
Regina Dahlhaus
The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1 , FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29593494/antiepileptogenic-effect-of-subchronic-palmitoylethanolamide-treatment-in-a-mouse-model-of-acute-epilepsy
#10
Julia M Post, Sebastian Loch, Raissa Lerner, Floortje Remmers, Ermelinda Lomazzo, Beat Lutz, Laura Bindila
Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA])...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29588947/the-intrahippocampal-kainate-mouse-model-of-mesial-temporal-lobe-epilepsy-lack-of-electrographic-seizure-like-events-in-sham-controls
#11
Friederike Twele, Alina Schidlitzki, Kathrin Töllner, Wolfgang Löscher
Objective: There is an ongoing debate about definition of seizures in experimental models of acquired epilepsy and how important adequate sham controls are in this respect. For instance, several mouse and rat strains exhibit high-voltage rhythmic spike or spike-wave discharges in the cortical electroencephalogram (EEG), which has to be considered when using such strains for induction of epilepsy by status epilepticus, traumatic brain injury, or other means. Mice developing spontaneous recurrent nonconvulsive and convulsive seizures after intrahippocampal injection of kainate are increasingly being used as a model of mesial temporal lobe epilepsy...
June 2017: Epilepsia Open
https://www.readbyqxmd.com/read/29587186/role-of-%C3%AE-2-3-specific-gaba-a-receptor-isoforms-in-the-development-of-hippocampus-kindling-epileptogenesis
#12
Doodipala Samba Reddy, Ryan F Yoshimura, Gunasekaran Ramanathan, Chase Carver, Timothy B Johnstone, Derk J Hogenkamp, Kelvin W Gee
OBJECTIVE: Subunit-specific positive allosteric modulators (PAMs) of gamma-aminobutyric acid-A (GABA-A) receptors are commonly used to uncover the role of GABA-A receptor isoforms in brain function. Recently, we have designed novel PAMs selective for β2/3 -subunit containing GABA-A receptors (β2/3 -selective PAMs) that are nonbenzodiazepine site-mediated and do not show an α-subunit isoform selectivity, yet exhibit anxiolytic efficacy with reduced potential for sedation, cognitive impairment, and tolerance...
March 24, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29558523/clustering-of-spontaneous-recurrent-seizures-separated-by-long-seizure-free-periods-an-extended-video-eeg-monitoring-study-of-a-pilocarpine-mouse-model
#13
Jung-Ah Lim, Jangsup Moon, Tae-Joon Kim, Jin-Sun Jun, Byeongsu Park, Jung-Ick Byun, Jun-Sang Sunwoo, Kyung-Il Park, Soon-Tae Lee, Keun-Hwa Jung, Ki-Young Jung, Manho Kim, Daejong Jeon, Kon Chu, Sang Kun Lee
Seizure clustering is a common and significant phenomenon in patients with epilepsy. The clustering of spontaneous recurrent seizures (SRSs) in animal models of epilepsy, including mouse pilocarpine models, has been reported. However, most studies have analyzed seizures for a short duration after the induction of status epilepticus (SE). In this study, we investigated the detailed characteristics of seizure clustering in the chronic stage of a mouse pilocarpine-induced epilepsy model for an extended duration by continuous 24/7 video-EEG monitoring...
2018: PloS One
https://www.readbyqxmd.com/read/29555850/electrophysiological-evidence-for-the-development-of-a-self-sustained-large-scale-epileptic-network-in-the-kainate-mouse-model-of-temporal-lobe-epilepsy
#14
Laurent Sheybani, Gwenaël Birot, Alessandro Contestabile, Margitta Seeck, Jozsef Zoltan Kiss, Karl Schaller, Christoph M Michel, Charles Quairiaux
Most research on focal epilepsy focuses on mechanisms of seizure generation in the primary epileptic focus (EF). However, neurological deficits that are not directly linked to seizure activity and that may persist after focus removal are frequent. The recruitment of remote brain regions of an epileptic network (EN) is recognized as a possible cause, but a profound lack of experimental evidence exists concerning their recruitment and the type of pathological activities they exhibit.We studied the development of epileptic activities at the large-scale in male mice of the kainate model of unilateral temporal lobe epilepsy using high-density surface EEG and multiple-site intracortical recordings...
March 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29546592/rna-polymerase-1-is-transiently-regulated-by-seizures-and-plays-a-role-in-a-pharmacological-kindling-model-of-epilepsy
#15
Aruna Vashishta, Lukasz P Slomnicki, Maciej Pietrzak, Scott C Smith, Murali Kolikonda, Shivani P Naik, Rosanna Parlato, Michal Hetman
Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region...
March 15, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29538625/protein-instability-haploinsufficiency-and-cortical-hyper-excitability-underlie-stxbp1-encephalopathy
#16
Jovana Kovacevic, Gregoire Maroteaux, Desiree Schut, Maarten Loos, Mohit Dubey, Julika Pitsch, Esther Remmelink, Bastijn Koopmans, James Crowley, L Niels Cornelisse, Patrick F Sullivan, Susanne Schoch, Ruud F Toonen, Oliver Stiedl, Matthijs Verhage
De novo heterozygous mutations in STXBP1/Munc18-1 cause early infantile epileptic encephalopathies (EIEE4, OMIM #612164) characterized by infantile epilepsy, developmental delay, intellectual disability, and can include autistic features. We characterized the cellular deficits for an allelic series of seven STXBP1 mutations and developed four mouse models that recapitulate the abnormal EEG activity and cognitive aspects of human STXBP1-encephalopathy. Disease-causing STXBP1 variants supported synaptic transmission to a variable extent on a null background, but had no effect when overexpressed on a heterozygous background...
March 12, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29497358/diffusion-basis-spectrum-and-diffusion-tensor-imaging-detect-hippocampal-inflammation-and-dendritic-injury-in-a-virus-induced-mouse-model-of-epilepsy
#17
Jie Zhan, Tsen-Hsuan Lin, Jane E Libbey, Peng Sun, Zezhong Ye, Chunyu Song, Michael Wallendorf, Honghan Gong, Robert S Fujinami, Sheng-Kwei Song
Hippocampal CA1 inflammation and dendritic loss are common in epilepsy. Quantitative detection of coexisting brain inflammation and injury could be beneficial in monitoring disease progression and assessing therapeutic efficacy. In this work, we used conventional diffusion tensor imaging (DTI, known to detect axonal injury and demyelination) and a novel diffusion basis spectrum imaging (DBSI, known to detect axonal injury, demyelination, and inflammation) to detect hippocampal CA1 lesions resulting from neuronal dendritic injury/loss and concomitant inflammation in Theiler's murine encephalomyelitis virus (TMEV)-induced seizure mice...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29495345/mesenchymal-stem-cell-protection-of-neurons-against-glutamate-excitotoxicity-involves-reduction-of-nmda-triggered-calcium-responses-and-surface-glur1-and-is-partly-mediated-by-tnf
#18
Irini Papazian, Vasiliki Kyrargyri, Maria Evangelidou, Anda Voulgari-Kokota, Lesley Probert
Mesenchymal stem cells (MSC) provide therapeutic effects in experimental CNS disease models and show promise as cell-based therapies for humans, but their modes of action are not well understood. We previously show that MSC protect rodent neurons against glutamate excitotoxicity in vitro, and in vivo in an epilepsy model. Neuroprotection is associated with reduced NMDA glutamate receptor (NMDAR) subunit expression and neuronal glutamate-induced calcium (Ca2+ ) responses, and increased expression of stem cell-associated genes...
February 25, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29481784/endophilin-a1-mediates-seizure-activity-via-regulation-of-ampars-in-a-ptz-kindled-epileptic-mouse-model
#19
Xinyuan Yu, Tao Xu, Shu Ou, Jinxian Yuan, Jing Deng, Rong Li, Juan Yang, Xi Liu, Qi Li, Yangmei Chen
Endophilin A1 is a member of the endophilin A family and is primarily expressed in the central nervous system. Endophilin A1 can mediate neuronal excitability by regulating neuronal synaptic plasticity, which indicates that the protein may be involved in epilepsy. However, to date, its role in epilepsy remains unclear. To explore the role of endophilin A1 in epilepsy, we aimed to investigate the expression patterns of endophilin A1 in patients with temporal lobe epilepsy (TLE) and in a pentylenetetrazole (PTZ)-kindled epileptic mouse model and to conduct behavioral and electrophysiological analyses after lentivirus-mediated knockdown of endophilin A1 in the hippocampus of epileptic mice...
February 23, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29476105/mtor-dependent-alterations-of-kv1-1-subunit-expression-in-the-neuronal-subset-specific-pten-knockout-mouse-model-of-cortical-dysplasia-with-epilepsy
#20
Lena H Nguyen, Anne E Anderson
Cortical dysplasia (CD) is a common cause for intractable epilepsy. Hyperactivation of the mechanistic target of rapamycin (mTOR) pathway has been implicated in CD; however, the mechanisms by which mTOR hyperactivation contribute to the epilepsy phenotype remain elusive. Here, we investigated whether constitutive mTOR hyperactivation in the hippocampus is associated with altered voltage-gated ion channel expression in the neuronal subset-specific Pten knockout (NS-Pten KO) mouse model of CD with epilepsy. We found that the protein levels of Kv1...
February 23, 2018: Scientific Reports
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