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epilepsy mouse model

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https://www.readbyqxmd.com/read/28098937/sodium-selenate-treatment-improves-symptoms-and-seizure-susceptibility-in-a-malin-deficient-mouse-model-of-lafora-disease
#1
Gentzane Sánchez-Elexpuru, José M Serratosa, Marina P Sánchez
OBJECTIVE: To search for new therapies aimed at ameliorating the neurologic symptoms and epilepsy developing in patients with Lafora disease. METHODS: Lafora disease is caused by loss-of-function mutations in either the EPM2A or EPM2B genes. Epm2a(-/-) and Epm2b(-/-) mice display neurologic and behavioral abnormalities similar to those found in patients. Selenium is a potent antioxidant and its deficiency has been related to the development of certain diseases, including epilepsy...
January 18, 2017: Epilepsia
https://www.readbyqxmd.com/read/28098336/preclinical-evaluation-of-intravenous-nax-810-2-a-novel-galr2-preferring-analog-for-anticonvulsant-efficacy-and-pharmacokinetics
#2
Cameron S Metcalf, Brian D Klein, Daniel R McDougle, Liuyin Zhang, Dan Kaufmann, Grzegorz Bulaj, H Steve White
OBJECTIVE: Potential clinical utility of galanin or peptidic analogs has been hindered by poor metabolic stability, lack of brain penetration, and hyperglycemia due to galanin receptor subtype 1 (GalR1) activation. NAX 810-2, a galanin receptor subtype 2 (GalR2)-preferring galanin analog, possesses 15-fold greater affinity for GalR2 over GalR1 and protects against seizures in the mouse 6 Hz, corneal kindling, and Frings audiogenic seizure models. The purpose of these studies was to further evaluate the preclinical efficacy and pharmacokinetics of NAX 810-2 in mice...
January 18, 2017: Epilepsia
https://www.readbyqxmd.com/read/28072448/identification-of-altered-brain-metabolites-associated-with-tnap-activity-in-a-mouse-model-of-hypophosphatasia-using-untargeted-nmr-based-metabolomics-analysis
#3
Thomas Cruz, Marie Gleizes, Stéphane Balayssac, Etienne Mornet, Grégory Marsal, José Luis Millán, Myriam Malet-Martino, Lionel G Nowak, Véronique Gilard, Caroline Fonta
Tissue Nonspecific Alkaline Phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However TNAP's role in the nervous system remains poorly understood. In order to investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28071688/epileptiform-activity-in-the-mouse-visual-cortex-interferes-with-cortical-processing-in-connected-areas
#4
L Petrucco, E Pracucci, M Brondi, G M Ratto, S Landi
Epileptiform activity is associated with impairment of brain function even in absence of seizures, as demonstrated by failures in various testing paradigm in presence of hypersynchronous interictal spikes (ISs). Clinical evidence suggests that cognitive deficits might be directly caused by the anomalous activity rather than by its underlying etiology. Indeed, we seek to understand whether ISs interfere with neuronal processing in connected areas not directly participating in the hypersynchronous activity in an acute model of epilepsy...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063983/loss-of-laforin-or-malin-results-in-increased-drp1-level-and-concomitant-mitochondrial-fragmentation-in-lafora-disease-mouse-models
#5
Mamta Upadhyay, Saloni Agarwal, Pratibha Bhadauriya, Subramaniam Ganesh
Lafora disease (LD) is an autosomal recessive form of a fatal disorder characterized by the myoclonus epilepsy, ataxia, psychosis, dementia, and dysarthria. A hallmark of LD is the presence of abnormal glycogen inclusions called Lafora bodies in the affected tissues including the neurons. LD can be caused by defects either in the laforin phosphatase coded by the EPM2A gene or in the malin E3 ubiquitin ligase coded by the NHLRC1 gene. The mouse models of LD, created by the targeted disruption of the LD genes, display several neurodegenerative changes...
January 4, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28053048/identifying-new-antiepileptic-drugs-through-genomics-based-drug-repurposing
#6
Nasir Mirza, Greame J Sills, Munir Pirmohamed, Anthony G Marson
Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28045139/chrna7-deficient-mice-manifest-no-consistent-neuropsychiatric-and-behavioral-phenotypes
#7
Jiani Yin, Wu Chen, Hongxing Yang, Mingshan Xue, Christian P Schaaf
The alpha7 nicotinic acetylcholine receptor, encoded by the CHRNA7 gene, has been implicated in various psychiatric and behavioral disorders, including schizophrenia, bipolar disorder, epilepsy, autism, Alzheimer's disease, and Parkinson's disease, and is considered a potential target for therapeutic intervention. 15q13.3 microdeletion syndrome is a rare genetic disorder, caused by submicroscopic deletions on chromosome 15q. CHRNA7 is the only gene in this locus that has been deleted entirely in cases involving the smallest microdeletions...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28042814/in-situ-real-time-monitoring-of-glutamate-and-electrophysiology-from-cortex-to-hippocampus-in-mice-based-on-a-microelectrode-array
#8
Xinyi Fan, Yilin Song, Yuanlin Ma, Song Zhang, Guihua Xiao, Lili Yang, Huiren Xu, Dai Zhang, Xinxia Cai
Changes in the structure and function of the hippocampus contribute to epilepsy, schizophrenia and other neurological or mental disorders of the brain. Since the function of the hippocampus depends heavily on the glutamate (Glu) signaling pathways, in situ real-time detection of Glu neurotransmitter release and electrophysiological signals in hippocampus is of great significance. To achieve the dual-mode detection in mouse hippocampus in vivo, a 16-channel implantable microelectrode array (MEA) was fabricated by micro-electromechanical system (MEMS) technology...
December 30, 2016: Sensors
https://www.readbyqxmd.com/read/28031221/molecular-magnetic-resonance-imaging-discloses-endothelial-activation-after-transient-ischaemic-attack
#9
Aurélien Quenault, Sara Martinez de Lizarrondo, Olivier Etard, Maxime Gauberti, Cyrille Orset, Benoît Haelewyn, Helen C Segal, Peter M Rothwell, Denis Vivien, Emmanuel Touzé, Carine Ali
SEE SUN ET AL DOI101093/AWW306 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: About 20% of patients with ischaemic stroke have a preceding transient ischaemic attack, which is clinically defined as focal neurological symptoms of ischaemic origin resolving spontaneously. Failure to diagnose transient ischaemic attack is a wasted opportunity to prevent recurrent disabling stroke. Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of a specific test. New diagnostic tools are thus needed, in particular for radiologically silent cases, which correspond to the recommended tissue-based definition of transient ischaemic attack...
January 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28028152/pharmacologic-inhibition-of-hsp90-to-prevent-glt-1-degradation-as-an-effective-therapy-for-epilepsy
#10
Longze Sha, Xueqin Wang, Jing Li, Xinze Shi, Liwen Wu, Yan Shen, Qi Xu
The glutamate transporter GLT-1 is critical for the maintenance of low interstitial glutamate concentrations. Loss of GLT-1 is commonly observed in neurological disorders, including temporal lobe epilepsy (TLE). Despite the hypothesis that targeting the mechanisms of GLT-1 deficiency may be a novel strategy for treating drug-resistant epilepsy, the underlying molecular cascade remains largely unknown. Here, we show that Hsp90β is up-regulated in reactive astrocytes of the epileptic hippocampus in patients with TLE and mouse models of epilepsy...
December 27, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28017800/viral-mouse-models-of-multiple-sclerosis-and-epilepsy-marked-differences-in-neuropathogenesis-following-infection-with-two-naturally-occurring-variants-of-theiler-s-virus-bean-strain
#11
Sonja Bröer, Elias Hage, Christopher Käufer, Ingo Gerhauser, Muneeb Anjum, Lin Li, Wolfgang Baumgärtner, Thomas F Schulz, Wolfgang Löscher
Following intracerebral inoculation, the BeAn 8386 strain of Theiler's virus causes persistent infection and inflammatory demyelinating encephalomyelitis in the spinal cord of T-cell defective SJL/J mice, which is widely used as a model of multiple sclerosis. In contrast, C57BL/6 (B6) mice clear the virus and develop inflammation and lesions in the hippocampus, associated with acute and chronic seizures, representing a novel model of viral encephalitis-induced epilepsy. Here we characterize the geno- and phenotype of two naturally occurring variants of BeAn (BeAn-1 and BeAn-2) that can be used to further understand the viral and host factors involved in the neuropathogenesis in B6 and SJL/J mice...
December 22, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28008324/vitamin-d3-for-the-treatment-of-epilepsy-basic-mechanisms-animal-models-and-clinical-trials
#12
REVIEW
Kevin Pendo, Christopher M DeGiorgio
There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Vitamin D3 is actively under investigation as a potential intervention for epilepsy. Vitamin D3 is fat-soluble steroid, which shows promise in animal models of epilepsy. Basic research has shed light on the possible mechanisms by which Vitamin D3 may reduce seizures, and animal data support the efficacy of Vitamin D3 in rat and mouse models of epilepsy...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/28007585/the-prrt2-knockout-mouse-recapitulates-the-neurological-diseases-associated-with-prrt2-mutations
#13
Caterina Michetti, Enrico Castroflorio, Ivan Marchionni, Nicola Forte, Bruno Sterlini, Francesca Binda, Floriana Fruscione, Pietro Baldelli, Flavia Valtorta, Federico Zara, Anna Corradi, Fabio Benfenati
Heterozygous and rare homozygous mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia episodic ataxia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function. Recently, an important role for PRTT2 in the neurotransmitter release machinery, brain development and synapse formation has been uncovered. In this work, we have characterized the phenotype of a mouse in which the PRRT2 gene has been constitutively inactivated (PRRT2 KO)...
December 20, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27998063/challenges-of-finding-novel-drugs-targeting-the-k-cl-cotransporter
#14
Eric Delpire, C David Weaver
Human disease-causing mutations and genetically modified mouse models have established the importance of KCC2 and KCC3 in nervous system physiology. These two proteins mediate the electroneutral cotransport of K(+) and Cl(-) ions across the neuronal membrane. Disruption of KCC2 function affects inhibitory synaptic transmission with consequences for epilepsy, pain perception, and potentially some neuropsychiatric disorders, whereas disruption of KCC3 affects both central and peripheral nervous systems, resulting in psychosis and peripheral neuropathy...
December 21, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27996351/effect-of-pregabalin-on-fear-based-conditioned-avoidance-learning-and-spatial-learning-in-a-mouse-model-of-scopolamine-induced-amnesia
#15
Kinga Sałat, Adrian Podkowa, Natalia Malikowska, Jędrzej Trajer
OBJECTIVES: Cognitive deficits are one of the frequent symptoms accompanying epilepsy or its treatment. METHODS: In this study the effect on cognition of intraperitoneally administered antiepileptic drug, pregabalin (10 mg/kg), was investigated in scopolamine-induced memory-impaired mice in the passive avoidance task and Morris water maze task. The effect of scopolamine and pregabalin on animals' locomotor activity was also studied. RESULTS: In the retention phase of the passive avoidance task, pregabalin reversed memory deficits induced by scopolamine (P < 0...
December 20, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27986596/effects-of-the-synthetic-neurosteroid-ganaxolone-on-seizure-activity-and-behavioral-deficits-in-an-angelman-syndrome-mouse-model
#16
Stephanie L Ciarlone, Xinming Wang, Michael A Rogawski, Edwin J Weeber
Angelman syndrome (AS) is a rare neurogenetic disorder characterized by severe developmental delay, motor impairments, and epilepsy. GABAergic dysfunction is believed to contribute to many of the phenotypic deficits seen in AS. We hypothesized that restoration of inhibitory tone mediated by extrasynaptic GABAA receptors could provide therapeutic benefit. Here, we report that ganaxolone, a synthetic neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, was anxiolytic, anticonvulsant, and improved motor deficits in the Ube3a-deficient mouse model of AS when administered by implanted mini-pump for 3 days or 4 weeks...
December 13, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27965624/ru486-mitigates-hippocampal-pathology-following-status-epilepticus
#17
Aynara C Wulsin, James P Herman, Steve C Danzer
Status epilepticus (SE) induces rapid hyper-activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. HPA axis hyperactivity results in excess exposure to high levels of circulating glucocorticoids, which are associated with neurotoxicity and depression-like behavior. These observations have led to the hypothesis that HPA axis dysfunction may exacerbate SE-induced brain injury. To test this hypothesis, we used the mouse pilocarpine model of epilepsy to determine whether use of the glucocorticoid receptor antagonist RU486 can attenuate hippocampal pathology following SE...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27959424/epha4-may-contribute-to-microvessel-remodeling-in-the-hippocampal-ca1-and-ca3-areas-in-a-mouse-model-of-temporal-lobe-epilepsy
#18
Li Feng, Yi Shu, Qian Wu, Tiantian Liu, Hongyu Long, Huan Yang, Yi Li, Bo Xiao
Unclustered and pre-clustered ephrin-A5-Fc have identical anti-epileptic effects in the dentate gyrus of hippocampus in a mouse model of temporal lobe epilepsy (TLE), and act through alleviating ephrin receptor A4 (EphA4)‑mediated neurogenesis and angiogenesis. However, the effects of ephrin‑A5‑Fcs on EphA4 and angiogenesis in Cornu Ammonis (CA)1 and CA3 areas remain unclear. In the present study, male C57BL/6 mice underwent pilocarpine‑induced TLE. The expression of EphA4 and ephrin‑A5 proteins was analyzed by immunohistochemistry, and the mean density and diameter of platelet endothelial cell adhesion molecule‑1‑labeled microvessels in CA1 and CA3 were calculated in the absence or presence of two types of ephrin‑A5‑Fc intrahippocampal infusion...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27957507/antibodies-to-inositol-1-4-5-triphosphate-receptor-1-in-patients-with-cerebellar-disease
#19
Penelope Fouka, Harry Alexopoulos, Ioanna Chatzi, Skarlatos G Dedos, Martina Samiotaki, George Panayotou, Panagiotis Politis, Athanasios Tzioufas, Marinos C Dalakas
OBJECTIVE: To describe newly identified autoantibodies associated with cerebellar disorders. DESIGN/METHODS: We first screened the sera of 15 patients with cerebellar ataxia, without any known associated autoantibodies, with immunocytochemistry on mouse brain. After characterization and validation of a newly identified antibody, 85 additional patients with suspected autoimmune cerebellar disease were screened using a cell-based assay. RESULTS: Immunoglobulin G from one of the first 15 patients demonstrated a distinct staining pattern on Purkinje neurons...
January 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27956120/intraperitoneal-injection-of-il-4-ifn-%C3%AE-modulates-the-proportions-of-microglial-phenotypes-and-improves-epilepsy-outcomes-in-a-pilocarpine-model-of-acquired-epilepsy
#20
Tianyi Li, Xuan Zhai, Jinqiu Jiang, Xiaojie Song, Wei Han, Jiannan Ma, Lingling Xie, Li Cheng, Hengsheng Chen, Li Jiang
Recent studies have reported microglia that are activated in the central nervous system (CNS) in patients with temporal lobe epilepsy and animal models of epilepsy. However, limited data are available on the dynamic changes of the proportions of various phenotypes of microglia throughout epileptogenesis and whether IL-4/IFN-γ administration can modulate the proportions of microglial phenotypes to affect the outcome of epilepsy. The current study examined this issue using a mouse model of pilocarpine-induced epilepsy...
December 9, 2016: Brain Research
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