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https://www.readbyqxmd.com/read/28334922/scn2a-deletion-improves-survival-and-brain-heart-dynamics-in-the-kcna1-null-mouse-model-of-sudden-unexpected-death-in-epilepsy-sudep
#1
Vikas Mishra, Bharat K Karumuri, Nicole M Gautier, Rui Liu, Timothy N Hutson, Stephanie L Vanhoof-Villalba, Ioannis Vlachos, Leonidas Iasemidis, Edward Glasscock
People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology, and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings...
March 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332054/a-mesiotemporal-lobe-epilepsy-mouse-model
#2
Duveau Venceslas, Roucard Corinne
Among the different forms of epilepsies, mesiotemporal lobe epilepsy (MTLE) is one of the most common and represents the main pharmaco-resistant form of epilepsy. There is therefore an urgent need to better understand this form of epilepsy to develop better anti-epileptic drugs. Many rodent models are mimicking some aspects of the human temporal lobe epilepsy but only few are addressing most of the human mesiotemporal lobe epilepsy. In this article, we describe the main characteristics of a mouse of model of mesial temporal lobe epilepsy...
March 23, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28331471/manipulating-micrornas-in-murine-models-targeting-the-multi-targeting-in-epilepsy
#3
David C Henshall
MicroRNAs are small noncoding RNAs that work posttranscriptionally to negatively regulate protein levels. They influence neuronal and glial structure and function, neuroinflammatory signaling, cell death, neurogenesis, and other processes relevant to epileptogenesis. Functional studies using oligonucleotide inhibitors (antagomirs) and mimics (agomirs) to modulate microRNAs in rat and mouse models of epilepsy show effects on evoked and spontaneous seizures and attendant neuropathology. The present review summarizes recent findings and points to gaps in our knowledge of the underlying mechanisms and directions for the future...
January 2017: Epilepsy Currents
https://www.readbyqxmd.com/read/28330876/electrocorticographic-dynamics-as-a-novel-biomarker-in-five-models-of-epileptogenesis
#4
Dan Z Milikovsky, Itai Weissberg, Lyna Solomon-Kamintsky, Kristina Lippmann, Osnat Schefenbauer, Federica Frigerio, Massimo Rizzi, Liron Sheintuch, Daniel Zelig, Jonathan Ofer, Annamaria Vezzani, Alon Friedman
Post injury epilepsy (PIE) is a devastating sequela of various brain insults. While recent studies offer novel insights into the mechanisms underlying epileptogenesis and discover potential preventive treatments, the lack of PIE biomarkers hinders the clinical implementation of such treatments. Here we explored the biomarker potential of different electrographic features in five models of PIE. Electrocorticographic or intrahippocampal recordings of epileptogenesis (from the insult to the first spontaneous seizure) from two laboratories were analyzed in 3 mouse and 2 rat PIE models...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28325299/potent-anti-seizure-effects-of-locked-nucleic-acid-antagomirs-targeting-mir-134-in-multiple-mouse-and-rat-models-of-epilepsy
#5
Cristina R Reschke, Luiz F Almeida Silva, Braxton A Norwood, Ketharini Senthilkumar, Gareth Morris, Amaya Sanz-Rodriguez, Ronán M Conroy, Lara Costard, Valentin Neubert, Sebastian Bauer, Michael A Farrell, Donncha F O'Brien, Norman Delanty, Stephanie Schorge, R Jeroen Pasterkamp, Felix Rosenow, David C Henshall
Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28303258/alterations-in-cytosolic-and-mitochondrial-u-13-c-glucose-metabolism-in-a-chronic-epilepsy-mouse-model
#6
Tanya S McDonald, Catalina Carrasco-Pozo, Mark P Hodson, Karin Borges
Temporal lobe epilepsy is a common form of adult epilepsy and shows high resistance to treatment. Increasing evidence has suggested that metabolic dysfunction contributes to the development of seizures, with previous studies indicating impairments in brain glucose metabolism. Here we aim to elucidate which pathways involved in glucose metabolism are impaired, by tracing the hippocampal metabolism of injected [U-(13)C]glucose (i.p.) during the chronic stage of the pilocarpine-status epilepticus mouse model of epilepsy...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28294308/neuronal-inhibition-and-seizure-suppression-by-acetoacetate-and-its-analog-2-phenylbutyrate
#7
Atsushi Kadowaki, Nagisa Sada, Narinobu Juge, Ayaka Wakasa, Yoshinori Moriyama, Tsuyoshi Inoue
OBJECTIVE: The ketogenic diet is clinically used to treat drug-resistant epilepsy. The diet treatment markedly increases ketone bodies (acetoacetate and β-hydroxybutyrate), which work as energy metabolites in the brain. Here, we investigated effects of acetoacetate on voltage-dependent Ca(2+) channels (VDCCs) in pyramidal cells of the hippocampus. We further explored an acetoacetate analog that inhibited VDCCs in pyramidal cells, reduced excitatory postsynaptic currents (EPSCs), and suppressed seizures in vivo...
March 11, 2017: Epilepsia
https://www.readbyqxmd.com/read/28290134/animal-models-of-seizures-and-epilepsy-past-present-and-future-role-for-the-discovery-of-antiseizure-drugs
#8
Wolfgang Löscher
The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. Except for some early treatments, including bromides and phenobarbital, the antiseizure activity of all clinically used drugs was, for the most part, defined by acute seizure models in rodents using the maximal electroshock and subcutaneous pentylenetetrazole seizure tests and the electrically kindled rat. Unfortunately, the clinical evidence to date would suggest that none of these models, albeit useful, are likely to identify those therapeutics that will effectively manage patients with drug resistant seizures...
March 13, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28277939/potassium-channel-expression-and-function-in-microglia-plasticity-and-possible-species-variations
#9
Hai M Nguyen, Linda V Blomster, Palle Christophersen, Heike Wulff
Potassium channels play important roles in microglia functions and thus constitute potential targets for the treatment of neurodegenerative diseases like Alzheimer, Parkinson and stroke. However, uncertainty still prevails as to which potassium channels are expressed and at what levels in different species, how the expression pattern changes upon activation with M1 or M2 polarizing stimuli compared with more complex exposure paradigms, and - most importantly - how these findings relate to the in vivo situation...
March 1, 2017: Channels
https://www.readbyqxmd.com/read/28272506/a-murine-model-to-study-epilepsy-and-sudep-induced-by-malaria-infection
#10
Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff
One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28269163/structural-and-functional-changes-during-epileptogenesis-in-the-mouse-model-of-medial-temporal-lobe-epilepsy
#11
Yvan Dietrich, Pierre-Antoine Eliat, Gabriel Dieuset, Herve Saint-Jalmes, Charles Pineau, Fabrice Wendling, Benoit Martin
An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28268645/effect-of-temperature-on-sleep-regulation-in-an-animal-epilepsy-model
#12
Asmaa Ajwad, Farid Yaghouby, Dillon Huffman, Bruce O'Hara, Sridhar Sunderam
Besides recurring seizures, disordered sleep is common in individuals with epilepsy and may present as reduced sleep depth, altered proportions of different stages of sleep, intermittent arousal, and other phenomena. Sleep loss can in turn precipitate seizures, thus sustaining a vicious cycle. It is well known that changes in ambient temperature elicit thermoregulatory responses that alter the dynamics of sleep. As a first step toward therapeutic sleep modulation for epilepsy, we assessed the effect of elevated ambient temperature on sleep dynamics and seizure yield in the chronic pilocarpine mouse model of temporal lobe epilepsy...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28242958/intranasal-delivery-of-mir-146a-mimics-delayed-seizure-onset-in-the-lithium-pilocarpine-mouse-model
#13
Hua Tao, Jianghao Zhao, Tingting Liu, Yujie Cai, Xu Zhou, Huaijie Xing, Yan Wang, Mingkang Yin, Wangtao Zhong, Zhou Liu, Keshen Li, Bin Zhao, Haihong Zhou, Lili Cui
Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28242676/voltage-sensitive-rhodol-with-enhanced-two-photon-brightness
#14
Rishikesh U Kulkarni, Daniel J Kramer, Narges Pourmandi, Kaveh Karbasi, Helen S Bateup, Evan W Miller
We have designed, synthesized, and applied a rhodol-based chromophore to a molecular wire-based platform for voltage sensing to achieve fast, sensitive, and bright voltage sensing using two-photon (2P) illumination. Rhodol VoltageFluor-5 (RVF5) is a voltage-sensitive dye with improved 2P cross-section for use in thick tissue or brain samples. RVF5 features a dichlororhodol core with pyrrolidyl substitution at the nitrogen center. In mammalian cells under one-photon (1P) illumination, RVF5 demonstrates high voltage sensitivity (28% ΔF/F per 100 mV) and improved photostability relative to first-generation voltage sensors...
February 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28239767/down-regulation-of-pin1-in-temporal-lobe-epilepsy-patients-and-mouse-model
#15
Lan Tang, Yanke Zhang, Guojun Chen, Yan Xiong, Xuefeng Wang, Binglin Zhu
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is a unique PPIase belonging to the parvulin family, and it isomerizes peptide bond between phospho-(Ser/Thr) and Pro. Pin1 has been linked to the pathogenesis of various human diseases; however, its exact biological functions remain unclear. The aim of the present study is to explore the expression pattern of Pin1 in patients with refractory epilepsy and in a chronic pilocarpine-induced epileptic mouse model. Using Western blot, immunofluorescence and immunoprecipitation analysis, we found that Pin1 protein was mainly distributed in neurons, demonstrated by colocalization with the dendritic marker, MAP2...
February 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28237622/theiler-s-murine-encephalomyelitis-virus-infection-of-sjl-j-and-c57bl-6j-mice-models-for-multiple-sclerosis-and-epilepsy
#16
REVIEW
Ana Beatriz DePaula-Silva, Tyler J Hanak, Jane E Libbey, Robert S Fujinami
Mouse models are great tools to study the mechanisms of disease development. Theiler's murine encephalomyelitis virus is used in two distinct viral infection mouse models to study the human diseases multiple sclerosis (MS) and epilepsy. Intracerebral (i.c.) infection of the SJL/J mouse strain results in persistent viral infection of the central nervous system and a MS-like disease, while i.c. infection of the C57BL/6J mouse strain results in acute seizures and epilepsy. Our understanding of how the immune system contributes to the development of two disparate diseases caused by the same virus is presented...
February 12, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28235423/spatiotemporal-progression-of-ubiquitin-proteasome-system-inhibition-after-status-epilepticus-suggests-protective-adaptation-against-hippocampal-injury
#17
Tobias Engel, Jaime Martinez-Villarreal, Christine Henke, Eva M Jimenez-Mateos, Amaya Sanz-Rodriguez, Mariana Alves, Yasmina Hernandez-Santana, Gary P Brennan, Aidan Kenny, Aoife Campbell, Jose J Lucas, David C Henshall
BACKGROUND: The ubiquitin-proteasome-system (UPS) is the major intracellular pathway leading to the degradation of unwanted and/or misfolded soluble proteins. This includes proteins regulating cellular survival, synaptic plasticity and neurotransmitter signaling; processes controlling excitability thresholds that are altered by epileptogenic insults. Dysfunction of the UPS has been reported to occur in a brain region- and cell-specific manner and contribute to disease progression in acute and chronic brain diseases...
February 24, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28233679/synthesis-and-biological-evaluation-of-novel-n3-substituted-dihydropyrimidine-derivatives-as-t-type-calcium-channel-blockers-and-their-efficacy-as-analgesics-in-mouse-models-of-inflammatory-pain
#18
Mohamed Teleb, Fang-Xiong Zhang, Junting Huang, Vinicius M Gadotti, Ahmed M Farghaly, Omaima M AboulWafa, Gerald W Zamponi, Hesham Fahmy
Low-voltage-activated calcium channels are important regulators of neurotransmission and membrane ion conductance. A plethora of intracellular events rely on their modulation. Accordingly, they are implicated in many disorders including epilepsy, Parkinson's disease, pain and other neurological diseases. Among different subfamilies, T-type calcium channels, and in particular the CaV3.2 isoform, were shown to be involved in nociceptive neurotransmission. The role of CaV3.2 in pain modulation was supported by demonstrating selective antisense oligonucleotide-mediated CaV3...
February 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28227392/structural-and-functional-changes-during-epileptogenesis-in-the-mouse-model-of-medial-temporal-lobe-epilepsy
#19
Yvan Dietrich, Pierre-Antoine Eliat, Gabriel Dieuset, Herve Saint-Jalmes, Charles Pineau, Fabrice Wendling, Benoit Martin, Yvan Dietrich, Pierre-Antoine Eliat, Gabriel Dieuset, Herve Saint-Jalmes, Charles Pineau, Fabrice Wendling, Benoit Martin, Pierre-Antoine Eliat, Charles Pineau, Benoit Martin, Gabriel Dieuset, Yvan Dietrich, Herve Saint-Jalmes, Fabrice Wendling
An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226825/effect-of-temperature-on-sleep-regulation-in-an-animal-epilepsy-model
#20
Asmaa Ajwad, Farid Yaghouby, Dillon Huffman, Bruce O'Hara, Sridhar Sunderam, Asmaa Ajwad, Farid Yaghouby, Dillon Huffman, Bruce O'Hara, Sridhar Sunderam, Dillon Huffman, Farid Yaghouby, Asmaa Ajwad, Bruce O'Hara, Sridhar Sunderam
Besides recurring seizures, disordered sleep is common in individuals with epilepsy and may present as reduced sleep depth, altered proportions of different stages of sleep, intermittent arousal, and other phenomena. Sleep loss can in turn precipitate seizures, thus sustaining a vicious cycle. It is well known that changes in ambient temperature elicit thermoregulatory responses that alter the dynamics of sleep. As a first step toward therapeutic sleep modulation for epilepsy, we assessed the effect of elevated ambient temperature on sleep dynamics and seizure yield in the chronic pilocarpine mouse model of temporal lobe epilepsy...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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