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https://www.readbyqxmd.com/read/28315465/early-preclinical-evaluation-of-dihydropyrimidin-thi-ones-as-potential-anticonvulsant-drug-candidates
#1
Mariana Matias, Gonçalo Campos, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
Although significant advances are occurring in epilepsy research, about 30% of epileptic patients are still inadequately controlled by standard drug therapy. For this reason, it continues to be important to develop new chemical entities through which epilepsy could be effectively controlled. In this study, the anticonvulsant activity of forty-two dihydropyrimidin(thi)ones was explored and their efficacy was evaluated in rodents against the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole tests...
March 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28303499/pregnane-x-receptor-not-nuclear-factor-kappa-b-up-regulates-p-glycoprotein-expression-in-the-brain-of-chronic-epileptic-rats-induced-by-kainic-acid
#2
Nian Yu, Yan-Fang Zhang, Kang Zhang, Yong-Fei Cheng, Hai-Yan Ma, Qing Di
Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28303498/validation-of-a-preclinical-drug-screening-platform-for-pharmacoresistant-epilepsy
#3
Melissa L Barker-Haliski, Kristina Johnson, Peggy Billingsley, Jennifer Huff, Laura J Handy, Rizvana Khaleel, Zhenmei Lu, Matthew J Mau, Timothy H Pruess, Carlos Rueda, Gerald Saunders, Tristan K Underwood, Fabiola Vanegas, Misty D Smith, Peter J West, Karen S Wilcox
The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28299629/inhibition-of-calcineurin-a-by-fk506-suppresses-seizures-and-reduces-the-expression-of-glun2b-in-membrane-fraction
#4
Yuetao Wen, Pengfei Fu, Kunlun Wu, Kaichuang Si, Yanfeng Xie, Wei Dan, Yan Zhan, Quanhong Shi
FK506, a calcineurin inhibitor, shows neuroprotective effects and has been associated with neurodegenerative diseases. Calcineurin A (CaNA), a catalytic subunit of calcineurin, mediates the dephosphorylation of various proteins. N-methyl-D-aspartate receptor (GluN) is closely related to epileptogenesis, and various phosphorylation sites of GluN2B, a regulatory subunit of the GluN complex, have different functions. Thus, we hypothesized that one of the potential anti-epileptic mechanisms of FK506 is mediated by its ability to promote the phosphorylation of GluN2B and reduce the expression of GluN2B in membrane fraction by down-regulating CaNA...
March 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28298884/physical-exercise-restores-the-generation-of-newborn-neurons-in-an-animal-model-of-chronic-epilepsy
#5
Fabricio N Mendonça, Luiz E C Santos, Antônio M Rodrigues, Sérgio Gomes da Silva, Ricardo M Arida, Gilcélio A da Silveira, Fulvio A Scorza, Antônio-Carlos G Almeida
Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28292736/increased-metalloproteinase-activity-in-the-hippocampus-following-status-epilepticus
#6
Deepti Dubey, Paulette A McRae, Elyse K Rankin-Gee, Esther Baranov, Luke Wandrey, Stephanie Rogers, Brenda E Porter
Increased neuronal plasticity and neuronal cell loss has been implicated in the development of epilepsy following injury. Parvalbumin fast spiking inhibitory interneurons have a robust extracellular matrix coating their cell bodies and the proximal dendrites called the perineuronal net (PNN). The role of the PNN is not clear but it has been implicated in closing of the critical period, altering seizure thresholds and providing neuronal protection from oxidative stress. The PNN is susceptible to degradation following a prolonged seizure and there is an increase in proteolytic-fragments of the PNN enriched proteoglycan aggrecan (Dzwonek et al...
March 1, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28290134/animal-models-of-seizures-and-epilepsy-past-present-and-future-role-for-the-discovery-of-antiseizure-drugs
#7
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/28280577/detecting-and-characterizing-high-frequency-oscillations-in-epilepsy-a-case-study-of-big-data-analysis
#8
Liang Huang, Xuan Ni, William L Ditto, Mark Spano, Paul R Carney, Ying-Cheng Lai
We develop a framework to uncover and analyse dynamical anomalies from massive, nonlinear and non-stationary time series data. The framework consists of three steps: preprocessing of massive datasets to eliminate erroneous data segments, application of the empirical mode decomposition and Hilbert transform paradigm to obtain the fundamental components embedded in the time series at distinct time scales, and statistical/scaling analysis of the components. As a case study, we apply our framework to detecting and characterizing high-frequency oscillations (HFOs) from a big database of rat electroencephalogram recordings...
January 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28275953/design-and-comparative-evaluation-of-the-anticonvulsant-profile-carbonic-anhydrate-inhibition-and-teratogenicity-of-novel-carbamate-derivatives-of-branched-aliphatic-carboxylic-acids-with-4-aminobenzensulfonamide
#9
David Bibi, Hafiz Mawasi, Alessio Nocentini, Claudiu T Supuran, Bogdan Wlodarczyk, Richard H Finnell, Meir Bialer
Epilepsy is one of the most common neurological diseases, with between 34 and 76 per 100,000 people developing epilepsy annually. Epilepsy therapy for the past 100(+) years is based on the use of antiepileptic drugs (AEDs). Despite the availability of more than twenty old and new AEDs, approximately 30% of patients with epilepsy are not seizure-free with the existing medications. In addition, the clinical use of the existing AEDs is restricted by their side-effects, including the teratogenicity associated with valproic acid that restricts its use in women of child-bearing age...
March 9, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28275159/enduring-memory-impairments-provoked-by-developmental-febrile-seizures-are-mediated-by-functional-and-structural-effects-of-neuronal-restrictive-silencing-factor
#10
Katelin P Patterson, Jeremy M Barry, Megan M Curran, Akanksha Singh-Taylor, Gary Brennan, Neggy Rismanchi, Matias Page, Yoav Noam, Gregory L Holmes, Tallie Z Baram
In a subset of children experiencing prolonged febrile seizures (FS), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST)...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28269577/sinusoidal-stimulation-trains-suppress-epileptiform-spikes-induced-by-4-ap-in-the-rat-hippocampal-ca1-region-in-vivo
#11
Zheshan Guo, Zhouyan Feng, Ying Yu, Wenjie Zhou, Zhaoxiang Wang, Xuefeng Wei
Deep brain stimulation (DBS) shows promises in the treatment of refractory epilepsy. Due to the complex causes of epilepsy, the mechanisms of DBS are still unclear. Depolarization block caused by the persistent excitation of neurons may be one of the possible mechanisms. To test the hypothesis, 4-aminopyridine (4-AP) was injected in rat hippocampal CA1 region in-vivo to induce epileptiform activity. Sinusoidal stimulation trains were applied to the afferent pathway (Schaffer collaterals) of CA1 region to suppress the epileptiform spikes...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28269576/detection-of-single-unit-spikes-during-orthodromic-high-frequency-stimulation-in-rat-hippocampus
#12
Zhaoxiang Wang, Zhouyan Feng, Ying Yu, Yufang Zhu, Zheshan Guo
Deep brain stimulation (DBS) has been used as a treatment of brain diseases such as Parkinson's disease and is a promising therapy for epilepsy. But the mechanisms of high frequency stimulation (HFS) used by DBS are still uncertain. In order to investigate the changes of action penitential firings of individual neurons (single unit activity, SUA) during the period of HFS, a new algorithm based on window detection was designed to detect spikes in broadband-frequency recording signals. The results show that orthodromic-HFS (O-HFS) could excite the neurons in CA1 regions, and the firing rate of interneurons and pyramidal neurons increased significantly...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28269213/behavior-of-superparamagnetic-nanoparticles-in-regard-of-brain-activity-a-proof-of-concept
#13
Pierre-Olivier Champagne, Dang Nguyen, Lionel Carmant, Alain Bouthillier, Nathalie T Sanon, Mohamad Sawan
The study of cerebral magnetic activity is very promising for the understanding and care of diseases involving impaired cerebral activity such as epilepsy. One of the main hurdle in the recording of cerebral magnetic activity is that the intensity of cerebral magnetic fields is very weak. In this regard, we explore another potential way to appreciate the magnetic cerebral activity using superparamagnetic nanoparticles. These particles react to magnetic fields and can aggregate under their influence. Being superparamagnetic, they are also visible on magnetic resonance imaging (MRI)...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28268683/effect-of-vagus-nerve-stimulation-on-neural-adaptation-in-thalamo-cortical-system-in-rats
#14
Tomoyo I Shiramatsu, Rie Hitsuyu, Kenji Ibayashi, Ryohei Kanzaki, Kensuke Kawai, Hirokazu Takahashi
Vagus nerve stimulation (VNS) is a therapy on medically refractory epilepsy, and recently reported to improve cognitive function including learning and memory. The thalamo-cortical system may underlie such VNS-induced cognitive improvements. Thus, the present study targeted the auditory cortex and thalamus in rats, and investigated whether and how VNS modulates stimulus-specific adaptation (SSA) of the neural activity in these nuclei. A depth electrode array recorded auditory evoked potentials from the auditory thalamus and cortex under an oddball paradigm either with or without VNS...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28267625/diffusion-tensor-mri-shows-progressive-changes-in-the-hippocampus-and-dentate-gyrus-after-status-epilepticus-in-rat-histological-validation-with-fourier-based-analysis
#15
Raimo A Salo, Tuukka Miettinen, Teemu Laitinen, Olli Gröhn, Alejandra Sierra
Imaging markers for monitoring disease progression, recovery, and treatment efficacy are a major unmet need for many neurological diseases, including epilepsy. Recent evidence suggests that diffusion tensor imaging (DTI) provides high microstructural contrast even outside major white matter tracts. We hypothesized that in vivo DTI could detect progressive microstructural changes in the dentate gyrus and the hippocampal CA3bc in the rat brain after status epilepticus (SE). To test this hypothesis, we induced SE with systemic kainic acid or pilocarpine in adult male Wistar rats and subsequently scanned them using in vivo DTI at five time-points: prior to SE, and 10, 20, 34, and 79 days post SE...
March 4, 2017: NeuroImage
https://www.readbyqxmd.com/read/28265714/a-short-history-of-the-5-ht2c-receptor-from-the-choroid-plexus-to-depression-obesity-and-addiction-treatment
#16
REVIEW
Jose M Palacios, Angel Pazos, Daniel Hoyer
This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5-HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [(3)H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography...
March 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28262846/antiseizure-effects-of-ketogenic-diet-on-seizures-induced-with-pentylenetetrazole-4-aminopyridine-and-strychnine-in-wistar-rats
#17
E O Sanya, A O Soladoye, O O Desalu, P M Kolo, L A Olatunji, J K Olarinoye
The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days...
March 6, 2017: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
https://www.readbyqxmd.com/read/28262662/epilepsy-and-intellectual-disability-linked-protein-shrm4-interaction-with-gababrs-shapes-inhibitory-neurotransmission
#18
Jonathan Zapata, Edoardo Moretto, Saad Hannan, Luca Murru, Anna Longatti, Davide Mazza, Lorena Benedetti, Matteo Fossati, Christopher Heise, Luisa Ponzoni, Pamela Valnegri, Daniela Braida, Mariaelvina Sala, Maura Francolini, Jeffrey Hildebrand, Vera Kalscheuer, Francesca Fanelli, Carlo Sala, Bernhard Bettler, Silvia Bassani, Trevor G Smart, Maria Passafaro
Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABAB receptors (GABABRs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABABR activity causing increased anxiety-like behaviour and susceptibility to seizures...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28262620/effects-of-jasminum-multiflorum-leaf-extract-on-rodent-models-of-epilepsy-motor-coordination-and-anxiety
#19
Jonas I Addae, Ramish Pingal, Kheston Walkins, Renee Cruickshank, Farid F Youssef, Shivananda B Nayak
Jasmine flowers and leaves are used extensively in folk medicine in different parts of the world to treat a variety of diseases. However, there are very few published reports on the neuropsychiatric effects of Jasmine extracts. Hence, the objectives of the present study were to examine the effects of an alcohol extract of Jasminum multiflorum leaves on topically-applied bicuculline (a model of acute simple partial epilepsy) and maximal electroshock (MES, a model of generalized tonic-clonic seizure) in male Sprague-Dawley rats...
February 28, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28242439/kv3-1-kv3-2-channel-positive-modulators-enable-faster-activating-kinetics-and-increase-firing-frequency-in-fast-spiking-gabaergic-interneurons
#20
Kim Boddum, Charlotte Hougaard, Julie Xiao-Ying Lin, Nadia Lybøl von Schoubye, Henrik Sindal Jensen, Morten Grunnet, Thomas Jespersen
Due to their fast kinetic properties, Kv3.1 voltage gated potassium channels are important in setting and controlling firing frequency in neurons and pivotal in generating high frequency firing of interneurons. Pharmacological activation of Kv3.1 channels may possess therapeutic potential for treatment of epilepsy, hearing disorders, schizophrenia and cognitive impairments. Here we thoroughly investigate the selectivity and positive modulation of the two small molecules, EX15 and RE01, on Kv3 channels. Selectivity studies, conducted in Xenopus laevis oocytes confirmed a positive modulatory effect of the two compounds on Kv3...
February 24, 2017: Neuropharmacology
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