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epilepsy mouse model

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https://www.readbyqxmd.com/read/28542864/circadian-clustering-of-spontaneous-epileptic-seizures-emerges-after-pilocarpine-induced-status-epilepticus
#1
Julika Pitsch, Albert J Becker, Susanne Schoch, Johannes Alexander Müller, Marco de Curtis, Vadym Gnatkovsky
OBJECTIVE: Seizures in mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis are thought to develop with various latency intervals after an initial transient brain insult. To study seizure dynamics after an initial transient precipitating insult in a systematic fashion, we utilized continuous video-electroencephalography (EEG) monitoring after the induction of status epilepticus (SE) in a mouse MTLE model. METHODS: Continuous 24/7 video/telemetric hippocampal EEG recordings in the systemic pilocarpine MTLE mouse model...
May 24, 2017: Epilepsia
https://www.readbyqxmd.com/read/28536304/abnormal-glycogen-chain-length-pattern-not-hyperphosphorylation-is-critical-in-lafora-disease
#2
Felix Nitschke, Mitchell A Sullivan, Peixiang Wang, Xiaochu Zhao, Erin E Chown, Ami M Perri, Lori Israelian, Lucia Juana-López, Paola Bovolenta, Santiago Rodríguez de Córdoba, Martin Steup, Berge A Minassian
Lafora disease (LD) is a fatal progressive epilepsy essentially caused by loss-of-function mutations in the glycogen phosphatase laforin or the ubiquitin E3 ligase malin. Glycogen in LD is hyperphosphorylated and poorly hydrosoluble. It precipitates and accumulates into neurotoxic Lafora bodies (LBs). The leading LD hypothesis that hyperphosphorylation causes the insolubility was recently challenged by the observation that phosphatase-inactive laforin rescues the laforin-deficient LD mouse model, apparently through correction of a general autophagy impairment...
May 23, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28526576/carvacrol-promotes-neuroprotection-in-the-mouse-hemiparkinsonian-model
#3
L M Dati, H Ulrich, C C Real, Z P Feng, H S Sun, L R Britto
Carvacrol is a monoterpene that has been linked to neuroprotection in several animal models of neurodegeneration, including ischemia, epilepsy and traumatic neuronal injury. In this study, we investigated the effects of carvacrol (i.p.) upon the neurodegeneration induced by 6-hydroxy-dopamine unilateral intrastriatal injections in mice. We have also used the cylinder test to assess the behavioral effects of carvacrol in that model of Parkinson's disease, and immunoblots to evaluate the levels of caspase-3 and TRPM7, one of major targets of carvacrol...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28521116/efficacy-of-anticonvulsant-substances-in-the-6hz-seizure-test-comparison-of-two-rodent-species
#4
Elise Esneault, Guillaume Peyon, Vincent Castagné
Usually performed in the mouse, the 6Hz seizure test is used for screening potential new anticonvulsant substances against complex partial seizures. Nevertheless, advanced models of temporal lobe epilepsy (TLE) are more often performed in rats, so that possible species-related differences may complicate the development of anticonvulsant substances. The aim of the present study was to evaluate the feasibility of adapting the 6Hz test in the rat. We first compared the effects of increasing current intensities for inducing seizures in the mouse and in the rat...
May 10, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28521115/anticonvulsant-profile-of-the-neuroactive-steroid-sge-516-in-animal-models
#5
Rebecca S Hammond, Alison L Althaus, Michael A Ackley, Carla Maciag, Gabriel Martinez Botella, Francesco G Salituro, Albert J Robichaud, James J Doherty
Despite the availability of multiple antiepileptic drugs (AED), failure to adequately control seizures is a challenge for approximately one third of epilepsy patients, and new therapies with a differentiated mechanism of action are needed. The neuroactive steroid, SGE-516, is a positive allosteric modulator of both gamma- and delta-containing GABAA receptors. This broad GABAA receptor activity differentiates neuroactive steroids like SGE-516 from benzodiazepines, a class of anticonvulsants which have been shown in vitro to selectively target gamma-subunit containing GABAA receptors...
May 7, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28520841/chronic-inflammatory-pain-impairs-mglur5-mediated-depolarization-induced-suppression-of-excitation-in-the-anterior-cingulate-cortex
#6
Baolin Guo, Jiaqi Wang, Han Yao, Keke Ren, Jing Chen, Jing Yang, Guohong Cai, Haiying Liu, Yunlong Fan, Wenting Wang, Shengxi Wu
The anterior cingulate cortex (ACC) is a critical hub for nociceptive perception and pain-related anxiety. Long-term synaptic plasticity in ACC was found to be important for chronic inflammatory pain and pain-related anxiety. As short-term synaptic plasticity, depolarization-induced suppression of excitation (DSE) is involved in several conditions, such as chronic stress, epilepsy, and autism. However, it is still unknown whether DSE in the ACC is involved in the central sensitization of pain and anxiety. Using a whole-cell patch clamp, calcium imaging, western blot, and behavioral testing, we found that DSE was induced by a 2 s depolarization in postsynaptic pyramidal cells in ACC...
May 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28506618/the-ptz-kindling-mouse-model-of-epilepsy-exhibits-exploratory-drive-deficits-and-aberrant-vta-dopamine-neuron-activity-in-both-familiar-and-novel-space
#7
Mahboubeh Ahmadi, Jean-Philippe Dufour, Erich Seifritz, Javad Mirnajafi-Zadeh, Bechara J Saab
Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration...
May 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28505490/heat-induced-temperature-dysregulation-and-seizures-in-dravet-syndrome-gefs-gabrg2-q390x-mice
#8
Timothy A Warner, Zhong Liu, Robert L Macdonald, Jing-Qiong Kang
It has been established that febrile seizures and its extended syndromes like generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome have been associated with mutations especially in SCN1A and GABRG2 genes. In patients, the onset of FS is likely due to the combined effect of temperature and inflammation in genetically vulnerable individuals because fever is often associated with infection. Much effort has been spent to understand the mechanisms underlying fever induction of seizures...
April 30, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28502704/ketogenic-diet-leads-to-o-glcnac-modification-in-the-btbr-t-tf-j-mouse-model-of-autism
#9
Christopher Newell, Virginia L Johnsen, Nellie C Yee, Warren J Xu, Matthias S Klein, Aneal Khan, Jong M Rho, Jane Shearer
BACKGROUND: Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBR(T+tf/j) (BTBR) mouse model of ASD...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28497109/hippocampal-tnf%C3%AE-signaling-contributes-to-seizure-generation-in-an-infection-induced-mouse-model-of-limbic-epilepsy
#10
Dipan C Patel, Glenna Wallis, E Jill Dahle, Pallavi B McElroy, Kyle E Thomson, Raymond J Tesi, David E Szymkowski, Peter J West, Roy M Smeal, Manisha Patel, Robert S Fujinami, H Steve White, Karen S Wilcox
Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler's murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28492982/adenosine-a1-receptors-play-an-important-protective-role-against-cognitive-impairment-and-long-term-potentiation-inhibition-in-a-pentylenetetrazol-mouse-model-of-epilepsy
#11
Qing Zhou, Suiqiang Zhu, Yuchen Guo, Lifei Lian, Qi Hu, Xiaoyan Liu, Feng Xu, Na Zhang, Huicong Kang
Epilepsy is a complicated neurological disorder that occurs worldwide and features several kinds of comorbidities in addition to recurrent seizures. One of the most common comorbidities is cognitive impairment, which seriously affects patients' quality of life. Through activating pre- and postsynaptic adenosine A1 receptors (A1Rs), adenosine has demonstrated anticonvulsant and neuroprotective effects in many epileptic animal models. However, whether the neuroprotective effect of A1Rs will protect cognition during epileptogenesis remains unknown...
May 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28491900/screening-of-conventional-anticonvulsants-in-a-genetic-mouse-model-of-epilepsy
#12
Nicole A Hawkins, Lyndsey L Anderson, Tracy S Gertler, Linda Laux, Alfred L George, Jennifer A Kearney
OBJECTIVE: Epilepsy is a common neurological disorder that affects 1% of the population. Approximately, 30% of individuals with epilepsy are refractory to treatment, highlighting the need for novel therapies. Conventional anticonvulsant screening relies predominantly on induced seizure models. However, these models may not be etiologically relevant for genetic epilepsies. Mutations in SCN1A are a common cause of Dravet Syndrome, a severe epileptic encephalopathy. Dravet syndrome typically begins in infancy with seizures provoked by fever and then progresses to include afebrile pleomorphic seizure types...
May 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28490738/model-guided-control-of-hippocampal-discharges-by-local-direct-current-stimulation
#13
Faten Mina, Julien Modolo, Fanny Recher, Gabriel Dieuset, Arnaud Biraben, Pascal Benquet, Fabrice Wendling
Neurostimulation is an emerging treatment for drug-resistant epilepsies when surgery is contraindicated. Recent clinical results demonstrate significant seizure frequency reduction in epileptic patients, however the mechanisms underlying this therapeutic effect are largely unknown. This study aimed at gaining insights into local direct current stimulation (LDCS) effects on hyperexcitable tissue, by i) analyzing the impact of electrical currents locally applied on epileptogenic brain regions, and ii) characterizing currents achieving an "anti-epileptic" effect (excitability reduction)...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28473802/the-subiculum-a-potential-site-of-ictogenesis-in-a-neonatal-seizure-model
#14
Xin-Xin Wang, Yong-Hua Li, Hai-Qing Gong, Pei-Ji Liang, Pu-Ming Zhang, Qin-Chi Lu
Studies have reported that the subiculum is one origin of interictal-like discharges in adult patients with temporal lobe epilepsy; however, whether the subiculum represents a site of ictogenesis for neonatal seizures remains unclear. In this study, multi-electrode recording techniques were used to record epileptiform discharges induced by low-Mg(2+) or high-K(+) artificial cerebrospinal fluid in neonatal mouse hippocampal slices, and the spatiotemporal dynamics of the epileptiform discharges were analyzed...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28473648/activity-clamp-provides-insights-into-paradoxical-effects-of-the-anti-seizure-drug-carbamazepine
#15
G Morris, M Leite, D M Kullmann, I Pavlov, S Schorge, G Lignani
A major challenge in experimental epilepsy research is to reconcile the effects of anti-epileptic drugs (AEDs) on individual neurons with their network-level actions. Highlighting this difficulty, it is unclear why carbamazepine (CBZ), a front-line AED with a known molecular mechanism, has been reported to increase epileptiform activity in several clinical and experimental studies. We confirmed in an in vitro mouse model (both sexes) that the frequency of interictal bursts increased following CBZ perfusion...
May 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28458102/ivabradine-attenuates-the-anticonvulsant-potency-of-lamotrigine-but-not-that-of-lacosamide-pregabalin-and-topiramate-in-the-tonic-clonic-seizure-model-in-mice
#16
Katarzyna M Sawicka, Katarzyna Załuska, Agnieszka Wawryniuk, Karolina Załuska-Patel, Michał Szczyrek, Bartłomiej Drop, Jadwiga Daniluk, Monika Szpringer, Dorota Żółkowska, Jarogniew J Łuszczki
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are involved not only in synaptic transmission and neuronal excitability under physiological conditions, but also in seizure activity. To determine the influence of ivabradine (an HCN channel inhibitor) on the anticonvulsant potency of four novel antiepileptic drugs (AEDs: lacosamide, lamotrigine, pregabalin and topiramate) in the mouse maximal electroshock-induced seizure (MES) model. Adult male albino Swiss mice were challenged with maximal electroconvulsions (electric current of 25mA delivered via auricular electrodes)...
April 22, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28455369/complement-c5ar1-signaling-promotes-polarization-and-proliferation-of-embryonic-neural-progenitor-cells-through-pkc%C3%AE
#17
Liam G Coulthard, Owen A Hawksworth, Rui Li, Anushree Balachandran, John D Lee, Farshid Sepehrband, Nyoman Kurniawan, Angela Jeanes, David G Simmons, Ernst Wolvetang, Trent M Woodruff
The complement system, typically associated with innate immunity, is emerging as a key controller of non-immune systems including in development, with recent studies linking complement mutations with neurodevelopmental disease. A key effector of the complement response is the activation fragment C5a which, through its receptor C5aR1, is a potent driver of inflammation. Surprisingly, C5aR1 is also expressed during early mammalian embryogenesis, however no clearly defined function is ascribed to C5aR1 in development...
April 28, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28449218/development-and-pharmacologic-characterization-of-the-rat-6-hz-model-of-partial-seizures
#18
Cameron S Metcalf, Peter J West, Kyle E Thomson, Sharon F Edwards, Misty D Smith, H S White, Karen S Wilcox
OBJECTIVE: The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. METHODS: A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis...
April 27, 2017: Epilepsia
https://www.readbyqxmd.com/read/28441341/a-long-term-treatment-with-arachidonyl-2-chloroethylamide-combined-with-valproate-increases-neurogenesis-in-a-mouse-pilocarpine-model-of-epilepsy
#19
Marta Andres-Mach, Mirosław Zagaja, Agnieszka Haratym-Maj, Radosław Rola, Maciej Maj, Joanna Haratym, Monika Dudra-Jastrzębska, Jarogniew J Łuszczki
Rational polytherapy in the treatment of refractory epilepsy has been the main therapeutic modality for several years. In treatment with two or more antiepileptic drugs (AEDs), it is of particular importance that AEDs be selected based on their high anticonvulsant properties, minimal side effects, and impact on the formation of new neurons. The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28425097/seizure-frequency-correlates-with-loss-of-dentate-gyrus-gabaergic-neurons-in-a-mouse-model-of-temporal-lobe-epilepsy
#20
Paul S Buckmaster, Emily Abrams, Xiling Wen
Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. This study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31-61 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24-36 days...
April 20, 2017: Journal of Comparative Neurology
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