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epilepsy mouse model

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https://www.readbyqxmd.com/read/27900948/prediction-of-antiepileptic-drug-treatment-outcomes-using-machine-learning
#1
Sinisa Colic, Robert G Wither, Min Lang, Liang Zhang, James H Eubanks, Berj L Bardakjian
OBJECTIVE: Antiepileptic drug (AED) treatments produce inconsistent outcomes, often necessitating patients to go through several drug trials until a successful treatment can be found. This study proposes the use of machine learning techniques to predict epilepsy treatment outcomes of commonly used AEDs. APPROACH: Machine learning algorithms were trained and evaluated using features obtained from intracranial electroencephalogram (iEEG) recordings of the epileptiform discharges observed in Mecp2-deficient mouse model of the Rett Syndrome...
November 30, 2016: Journal of Neural Engineering
https://www.readbyqxmd.com/read/27895554/systemic-radical-scavenger-treatment-of-a-mouse-model-of-rett-syndrome-merits-and-limitations-of-the-vitamin-e-derivative-trolox
#2
Oliwia A Janc, Marc A Hüser, Katharina Dietrich, Belinda Kempkes, Christiane Menzfeld, Swen Hülsmann, Michael Müller
Rett syndrome (RTT) is a severe neurodevelopmental disorder typically arising from spontaneous mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2) gene. The almost exclusively female Rett patients show an apparently normal development during their first 6-18 months of life. Subsequently, cognitive- and motor-impairment, hand stereotypies, loss of learned skills, epilepsy and irregular breathing manifest. Early mitochondrial impairment and oxidative challenge are considered to facilitate disease progression...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27894304/brain-inflammation-is-accompanied-by-peripheral-inflammation-in-cstb-mice-a-model-for-progressive-myoclonus-epilepsy
#3
Olesya Okuneva, Zhilin Li, Inken Körber, Saara Tegelberg, Tarja Joensuu, Li Tian, Anna-Elina Lehesjoki
Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb (-/-) ) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb (-/-) mice in more detail...
November 28, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27891080/enhanced-burst-suppression-and-disruption-of-local-field-potential-synchrony-in-a-mouse-model-of-focal-cortical-dysplasia-exhibiting-spike-wave-seizures
#4
Anthony J Williams, Chen Zhou, Qian-Quan Sun
Focal cortical dysplasias (FCDs) are a common cause of brain seizures and are often associated with intractable epilepsy. Here we evaluated aberrant brain neurophysiology in an in vivo mouse model of FCD induced by neonatal freeze lesions (FLs) to the right cortical hemisphere (near S1). Linear multi-electrode arrays were used to record extracellular potentials from cortical and subcortical brain regions near the FL in anesthetized mice (5-13 months old) followed by 24 h cortical electroencephalogram (EEG) recordings...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27876882/nr4a1-knockdown-suppresses-seizure-activity-by-regulating-surface-expression-of-nr2b
#5
Yanke Zhang, Guojun Chen, Baobing Gao, Yunlin Li, Shuli Liang, Xiaofei Wang, Xuefeng Wang, Binglin Zhu
Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872690/the-effects-of-kainic-acid-induced-seizure-on-gene-expression-of-brain-neurotransmitter-receptors-in-mice-using-rt-2-pcr-array
#6
Taghi Naserpour Farivar, Marjan Nassiri-Asl, Pouran Johari, Reza Najafipour, Farid Hajiali
INTRODUCTION: Kainic acid (KA) induces neuropathological changes in specific regions of the mouse hippocampus comparable to changes seen in patients with chronic temporal lobe epilepsy (TLE). According to different studies, the expression of a number of genes are altered in the adult rat hippocampus after status epilepticus (SE) induced by KA. This study aimed to quantitatively evaluate changes in the gene expression of brain neurotransmitter receptors one week after administration of kainic acid in the mouse hippocampus...
October 2016: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/27861538/development-and-validation-of-a-new-mouse-model-to-investigate-the-role-of-sv2a-in-epilepsy
#7
Catherine Menten-Dedoyart, Maria Elisa Serrano Navacerrada, Odile Bartholome, Judit Sánchez Gil, Virginie Neirinckx, Sabine Wislet, Guillaume Becker, Alain Plenevaux, Priscilla Van den Ackerveken, Bernard Rogister
SV2A is a glycoprotein present in the membranes of most synaptic vesicles. Although it has been highly conserved throughout evolution, its physiological role remains largely unknown. Nevertheless, Levetiracetam, a very effective anti-epileptic drug, has been recently demonstrated to bind to SV2A. At present, our understanding of the normal function of SV2A and its possible involvement in diseases like epilepsy is limited. With this study, we sought to develop a relevant model enabling analysis of SV2A's role in the occurrence or progression of epilepsy...
2016: PloS One
https://www.readbyqxmd.com/read/27852007/apc-conditional-knock-out-mouse-is-a-model-of-infantile-spasms-with-elevated-neuronal-%C3%AE-catenin-levels-neonatal-spasms-and-chronic-seizures
#8
Antonella Pirone, Jon Alexander, Lauren A Lau, David Hampton, Andrew Zayachkivsky, Amy Yee, Audrey Yee, Michele H Jacob, Chris G Dulla
Infantile spasms (IS) are a catastrophic childhood epilepsy syndrome characterized by flexion-extension spasms during infancy that progress to chronic seizures and cognitive deficits in later life. The molecular causes of IS are poorly defined. Genetic screens of individuals with IS have identified multiple risk genes, several of which are predicted to alter β-catenin pathways. However, evidence linking malfunction of β-catenin pathways and IS is lacking. Here, we show that conditional deletion in mice of the adenomatous polyposis coli gene (APC cKO), the major negative regulator of β-catenin, leads to excessive β-catenin levels and multiple salient features of human IS...
November 13, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27836728/altered-gene-expression-profile-in-a-mouse-model-of-scn8a-encephalopathy
#9
Ryan S Sprissler, Jacy L Wagnon, Rosie K Bunton-Stasyshyn, Miriam H Meisler, Michael F Hammer
SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures...
November 9, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27836684/ketogenic-diets-improve-behaviors-associated-with-autism-spectrum-disorder-in-a-sex-specific-manner-in-the-el-mouse
#10
David N Ruskin, Jessica A Fortin, Subrina N Bisnauth, Susan A Masino
The core symptoms of autism spectrum disorder are poorly treated with current medications. Symptoms of autism spectrum disorder are frequently comorbid with a diagnosis of epilepsy and vice versa. Medically-supervised ketogenic diets are remarkably effective nonpharmacological treatments for epilepsy, even in drug-refractory cases. There is accumulating evidence that supports the efficacy of ketogenic diets in treating the core symptoms of autism spectrum disorders in animal models as well as limited reports of benefits in patients...
January 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/27810516/is-fgf13-a-major-contributor-to-genetic-epilepsy-with-febrile-seizures-plus
#11
Kristin A Rigbye, Peter M van Hasselt, Rosemary Burgess, John A Damiano, Saul A Mullen, Slavé Petrovski, Ram S Puranam, Koen L I van Gassen, Jozef Gecz, Ingrid E Scheffer, James O McNamara, Samuel F Berkovic, Michael S Hildebrand
Mutation of fibroblast growth factor 13 (FGF13) has recently been implicated in genetic epilepsy with febrile seizures plus (GEFS+) in a single family segregating a balanced translocation with a breakpoint in this X chromosome gene, predicting a partial knockout involving 3 of 5 known FGF13 isoforms. Investigation of a mouse model of complete Fgf13 knock-out revealed increased susceptibility to hyperthermia-induced seizures and epilepsy. Here we investigated whether mutation of FGF13 would explain other cases of GEFS+ compatible with X-linked inheritance...
December 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27800651/crocin-attenuates-kindling-development-and-associated-cognitive-impairments-in-mice-via-inhibiting-reactive-oxygen-species-mediated-nf-%C3%AE%C2%BAb-activation
#12
Arindam Ghosh Mazumder, Pallavi Sharma, Vikram Patial, Damanpreet Singh
Crocin is a pharmacologically active carotenoid pigment mainly present in the stigmas of Crocus sativus L. (Iridaceae). It has been well explored in experimental animal models of cognitive impairments, depression, anxiety and epilepsy. The present study was designed to understand the effect of crocin on pentylenetetrazol (PTZ)-induced kindling development and its associated cognitive deficit in mouse. Crocin treatment at 5, 10 and 20 mg/kg p.o. doses showed marked reduction in severity of PTZ-induced seizures...
October 31, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27799911/huperzine-a-provides-robust-and-sustained-protection-against-induced-seizures-in-scn1a-mutant-mice
#13
Jennifer C Wong, Stacey B B Dutton, Stephen D Collins, Steven Schachter, Andrew Escayg
De novo loss-of-function mutations in the voltage-gated sodium channel (VGSC) SCN1A (encoding Nav1.1) are the main cause of Dravet syndrome (DS), a catastrophic early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), refractory afebrile epilepsy, cognitive and behavioral deficits, and a 15-20% mortality rate. SCN1A mutations also lead to genetic epilepsy with febrile seizures plus (GEFS+), which is an inherited disorder characterized by early-life FSs and the development of a range of adult epilepsy subtypes...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27791149/cardiac-arrhythmia-in-a-mouse-model-of-sodium-channel-scn8a-epileptic-encephalopathy
#14
Chad R Frasier, Jacy L Wagnon, Yangyang Oliver Bao, Luke G McVeigh, Luis F Lopez-Santiago, Miriam H Meisler, Lori L Isom
: Patients with early infantile epileptic encephalopathy (EIEE) are at increased risk for sudden unexpected death in epilepsy (SUDEP). De novo mutations of the sodium channel gene SCN8A, encoding the sodium channel Nav1.6, result in EIEE13 (OMIM 614558), which has a 10% risk of SUDEP. Here, we investigated the cardiac phenotype of a mouse model expressing the gain of function EIEE13 patient mutation p.Asn1768Asp in Scn8a (Nav1.6-N1768D). We tested Scn8a(N1768D/+) mice for alterations in cardiac excitability...
October 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27768696/fine-mapping-of-a-dravet-syndrome-modifier-locus-on-mouse-chromosome-5-and-candidate-gene-analysis-by-rna-seq
#15
Nicole A Hawkins, Nicole J Zachwieja, Alison R Miller, Lyndsey L Anderson, Jennifer A Kearney
A substantial number of mutations have been identified in voltage-gated sodium channel genes that result in various forms of human epilepsy. SCN1A mutations result in a spectrum of severity ranging from mild febrile seizures to Dravet syndrome, an infant-onset epileptic encephalopathy. Dravet syndrome patients experience multiple seizures types that are often refractory to treatment, developmental delays, and elevated risk for SUDEP. The same sodium channel mutation can produce epilepsy phenotypes of varying clinical severity...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27748060/developmental-regulation-of-rna-processing-by-rbfox-proteins
#16
John G Conboy
The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3'UTRs, and pre-miRNAs hairpin structures. Versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing...
October 17, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27745527/association-between-mossy-fiber-sprouting-and-expression-of-semaphorin-3f-protein-in-dentate-gyrus-of-hippocampus-in-lithium-pilocarpine-induced-status-epilepticus-mouse-model
#17
Xiaodong Cai, Ling Long, Libai Yang, Ziyi Chen, Guanzhong Ni, Jiaming Qin, Jueqian Zhou, Liemin Zhou
OBJECTIVES: Mossy fiber sprouting is involved in the pathogenesis of mesial temporal lobe epilepsy. But the exact mechanism of formation of mossy fiber sprouting is still unclear. Semaphorin-3f protein could inhibit the growth of neuron axons. The aim of this research is to evaluate the association between semaphorin-3f expression and mossy fiber sprouting. METHODS: We established pilocarpine-induced status epilepticus (PISE) models firstly. Then, mossy fiber sprouting in the hippocampus of PISE models was examined by Timm staining...
October 17, 2016: Neurological Research
https://www.readbyqxmd.com/read/27744244/distinct-behavioral-and-epileptic-phenotype-differences-in-129-p-mice-compared-to-c57bl-6-mice-subject-to-intraamygdala-kainic-acid-induced-status-epilepticus
#18
Luiz Fernando Almeida Silva, Tobias Engel, Cristina R Reschke, Ronan M Conroy, Elena Langa, David C Henshall
Animal models of status epilepticus are important tools to understand the pathogenesis of epileptic brain injury and evaluate potential seizure-suppressive, neuroprotective, and antiepileptogenic treatments. Focal elicitation of status epilepticus by intraamygdala kainic acid in mice produces unilateral hippocampal damage and the emergence of spontaneous recurrent seizures after a short latent period. The model has been characterized in C57BL/6, BALB/c, and SJL mice where strain-specific differences were found in the extent of hippocampal damage...
October 13, 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27743549/serotonergic-agents-act-on-5-ht3-receptors-in-the-brain-to-block-seizure-induced-respiratory-arrest-in-the-dba-1-mouse-model-of-sudep
#19
Carl L Faingold, Marcus Randall, Chang Zeng, Shifang Peng, Xiaoyan Long, Hua-Jun Feng
Drugs that enhance the action of serotonin (5-hydroxytrypamine, 5-HT), including several selective serotonin reuptake inhibitors (SSRIs), reduce susceptibility to seizure-induced respiratory arrest (S-IRA) that leads to death in the DBA/1 mouse model of sudden unexpected death in epilepsy (SUDEP). However, it is not clear if specific 5-HT receptors are important in the action of these drugs and whether the brain is the major site of action of these agents in this SUDEP model. The current study examined the actions of agents that affect the 5-HT3 receptor subtype on S-IRA and whether intracerebroventricular (ICV) microinjection of an SSRI would reduce S-IRA susceptibility in DBA/1 mice...
November 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27739854/time-evolution-of-interhemispheric-coupling-in-a-model-of-focal-neocortical-epilepsy-in-mice
#20
F Vallone, E Vannini, A Cintio, M Caleo, A Di Garbo
Epilepsy is characterized by substantial network rearrangements leading to spontaneous seizures and little is known on how an epileptogenic focus impacts on neural activity in the contralateral hemisphere. Here, we used a model of unilateral epilepsy induced by injection of the synaptic blocker tetanus neurotoxin (TeNT) in the mouse primary visual cortex (V1). Local field potential (LFP) signals were simultaneously recorded from both hemispheres of each mouse in acute phase (peak of toxin action) and chronic condition (completion of TeNT effects)...
September 2016: Physical Review. E
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