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Epileptogenesis

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https://www.readbyqxmd.com/read/28822838/scavenging-reactive-oxygen-species-inhibits-status-epilepticus-induced-neuroinflammation
#1
Pallavi B McElroy, Li-Ping Liang, Brian J Day, Manisha Patel
Inflammation has been identified as an important mediator of seizures and epileptogenesis. Understanding the mechanisms underlying seizure-induced neuroinflammation could lead to the development of novel therapies for the epilepsies. Reactive oxygen species (ROS) are recognized as mediators of seizure-induced neuronal damage and are known to increase in models of epilepsies. ROS are also known to contribute to inflammation in several disease states. We hypothesized that ROS are key modulators of neuroinflammation i...
August 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28818511/vitamin-d-enhances-antiepileptic-and-cognitive-effects-of-lamotrigine-in-pentylenetetrazole-kindled-rats
#2
Ali F Abdel-Wahab, Mohamed A Afify, Amal M Mahfouz, Naiyer Shahzad, Ghazi A Bamagous, Saeed S Al Ghamdi
Despite long use of antiepileptic drugs, it remains a challenge to achieve seizure control while reducing adverse effects and preventing cognitive impairment. Several lines of evidence suggest a role of vitamin D in epilepsy. So this study aimed to investigate the effect of vitamin D on epileptogenesis, cognitive dysfunction and antiepileptic activity of lamotrigine, in a rat model of chemical kindling. Rats were kindled by pentylenetetrazole injections every other day over four weeks, together with daily oral treatment by either vehicle, vitamin D, lamotrigine or combination of vitamin D and lamotrigine...
August 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28814872/microrna-expression-profiles-in-chronic-epilepsy-rats-and-neuroprotection-from-seizures-by-targeting-mir-344a
#3
Xixia Liu, Yuhan Liao, Xiuxiu Wang, Donghua Zou, Chun Luo, Chongdong Jian, Yuan Wu
MicroRNA (miRNA) is believed to play a crucial role in the cause and treatment of epilepsy by controlling gene expression. However, it is still unclear how miRNA profiles change after multiple prolonged seizures and aggravation of brain injury in chronic epilepsy (CE). To investigate the role of miRNA in epilepsy, we utilized the CE rat models with pentylenetetrazol (PTZ) and miRNA profiles in the hippocampus. miRNA profiles were characterized using miRNA microarray analysis and were compared with the rats in the sham group, which received 0...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28799516/antiepileptic-drugs-in-clinical-development-differentiate-or-die
#4
Gaetano Zaccara, D Schmidt
BACKGROUND: Animal models when carefully selected, designed and conducted, are important parts of any translational drug development strategy. However, research of new compounds for patients with drug-resistant epilepsies is still based on animal experiments, mostly in rodents, which are far from being a model of chronic human epilepsy and have failed to differentiate the efficacy of new compounds versus standard drug treatment. Objective The objective was identification and description of compounds in clinical development in 2016...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28791347/dysregulation-of-zinc-lipid-metabolism%C3%A2-associated-genes-in-the-rat-hippocampus-and-cerebral-cortex-in-early-adulthood-following-recurrent-neonatal-seizures
#5
Zhen-Hong Li, Li-Li Li, Mei-Fang Jin, Xu-Qin Chen, Qi Sun, Hong Ni
Although it has been established that recurrent or prolonged clinical seizures during infancy may cause lifelong brain damage, the underlying molecular mechanism is still not well elucidated. The present study, to the best of our knowledge, is the first to investigate the expression of twenty zinc (Zn)/lipid metabolism‑associated genes in the hippocampus and cerebral cortex of rats following recurrent neonatal seizures. In the current study, 6‑day‑old Sprague‑Dawley rats were randomly divided into control (CONT) and recurrent neonatal seizure (RS) groups...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28783762/using-postmortem-hippocampi-tissue-can-interfere-with-differential-gene-expression-analysis-of-the-epileptogenic-process
#6
João Paulo Lopes Born, Heloisa de Carvalho Matos, Mykaella Andrade de Araujo, Olagide Wagner Castro, Marcelo Duzzioni, José Eduardo Peixoto-Santos, João Pereira Leite, Norberto Garcia-Cairasco, Maria Luisa Paçó-Larson, Daniel Leite Góes Gitaí
Neuropathological studies often use autopsy brain tissue as controls to evaluate changes in protein or RNA levels in several diseases. In mesial temporal lobe epilepsy (MTLE), several genes are up or down regulated throughout the epileptogenic and chronic stages of the disease. Given that postmortem changes in several gene transcripts could impact the detection of changes in case-control studies, we evaluated the effect of using autopsy specimens with different postmortem intervals (PMI) on differential gene expression of the Pilocarpine (PILO)induced Status Epilepticus (SE) of MTLE...
2017: PloS One
https://www.readbyqxmd.com/read/28781107/epileptogenesis-meets-occam-s-razor
#7
REVIEW
Robert S Sloviter
Pharmacological treatment to prevent brain injury-induced temporal lobe epileptogenesis has been generally unsuccessful, raising the issues of exactly when the conversion process to an epileptic brain state occurs and reaches completion, and which cellular or network processes might be the most promising therapeutic targets. The time course of epileptogenesis is a central issue, with recent results suggesting that injury-induced epileptogenesis can be a much more rapid process than previously thought, and may be inconsistent with a delayed epileptogenic mechanism...
August 3, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28777257/chronic-levetiracetam-decreases-hippocampal-and-testicular-aromatase-expression-in-normal-but-not-kainic-acid-induced-experimental-model-of-acute-seizures-in-rats
#8
Mehtap Cincioğlu-Palabiyik, Meral Üner, Dilek Ertoy-Baydar, Yildirim Sara, Hande Karahan, Pelin Kelicen-Uğur
Reproductive disorders are more common in men with epilepsy taking anticonvulsant medications. Antiseizure/anticonvulsant drugs and seizures in medial temporal lobe structures may cause gonadal dysfunction, including infertility, decreased libido, and potency. Levels of circulating bioavailable testosterone are affected by the aromatase enzyme, which converts testosterone into estrogen and may be affected by seizure medications. However, the relationship of anticonvulsant drugs with central aromatase levels is not clear...
August 2, 2017: Neuroreport
https://www.readbyqxmd.com/read/28772144/epileptic-rat-brain-tissue-analyzed-by-2d-correlation-raman-spectroscopy
#9
Julia Sacharz, Aleksandra Wesełucha-Birczyńska, Janina Zięba-Palus, Marian H Lewandowski, Rafał Kowalski, Katarzyna Palus, Łukasz Chrobok, Paulina Moskal, Malwina Birczyńska, Agnieszka Sozańska
Absence epilepsy is the neurological disorder characterized by the pathological spike-and wave discharges present in the electroencephalogram, accompanying a sudden loss of consciousness. Experiments were performed on brain slices obtained from young male WAG/Rij rats (2-3weeks old), so that they were sampled before the appearance of brain-damaging seizures symptoms. Two differing brain areas of the rats' brain tissue were studied: the somatosensory cortex (Sc) and the dorsal lateral geniculate nucleus of the thalamus (DLG)...
July 25, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28762469/impairment-of-gabaergic-system-contributes-to-epileptogenesis-in-glutaric-acidemia-type-i
#10
Mayara Vendramin Pasquetti, Letícia Meier, Samanta Loureiro, Marcelo Ganzella, Bernardo Junges, Letícia Barbieri Caus, Alexandre Umpierrez Amaral, David M Koeller, Stephen Goodman, Michael Woontner, Diogo Onofre Gomes de Souza, Moacir Wajner, Maria Elisa Calcagnotto
OBJECTIVES: Glutaric acidemia type I (GA-I) is an inherited neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) and characterized by increased levels of glutaric, 3-OH-glutaric, and glutaconic acids in the brain parenchyma. The increment of these organic acids inhibits glutamate decarboxylase (GAD) and consequently lowers the γ-aminobutyric acid (GABA) synthesis. Untreated patients exhibit severe neurologic deficits during development, including epilepsy, especially following an acute encephalopathy outbreak...
August 1, 2017: Epilepsia
https://www.readbyqxmd.com/read/28758946/hippocampal-proteome-of-rats-subjected-to-the-li-pilocarpine-epilepsy-model-and-the-effect-of-carisbamate-treatment
#11
José Eduardo Marques-Carneiro, Daniele Suzete Persike, Julia Julie Litzahn, Jean-Christophe Cassel, Astrid Nehlig, Maria José da Silva Fernandes
In adult rats, the administration of lithium-pilocarpine (LiPilo) reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE). Carisbamate (CRS) possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment...
July 30, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28753467/the-association-of-scn1a-p-thr1067ala-polymorphism-with-epilepsy-risk-and-the-response-to-antiepileptic-drugs-in-slovenian-children-and-adolescents-with-epilepsy
#12
Sara Bertok, Vita Dolžan, Katja Goričar, Katarina Trebušak Podkrajšek, Tadej Battelino, Zvonka Rener-Primec
PURPOSE: The voltage-gated sodium channel SCN1A mutations are involved in epileptogenesis and may be associated with different epilepsy phenotypes. The SCN1A channel is also an important antiepileptic drug (AED) target. The aim of this study was to investigate if the SCN1A c.3184A>G/p.Thr1067Ala polymorphism modifies the epilepsy risk or is associated with the responsiveness to AEDs in Slovenian children and adolescents with epilepsy. METHODS: In total, 216 paediatric patients with epilepsy were consecutively recruited during routine outpatient follow-up visits between January 2011 and December 2014...
July 20, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28749594/seizure-activity-per-se-does-not-induce-tissue-damage-markers-in-human-neocortical-focal-epilepsy
#13
Laura Rossini, Rita Garbelli, Vadym Gnatkovsky, Giuseppe Didato, Flavio Villani, Roberto Spreafico, Francesco Deleo, Giorgio Lo Russo, Giovanni Tringali, Francesca Gozzo, Laura Tassi, Marco de Curtis
Objective The contribute of recurring seizures to the progression of epileptogenesis is debated. Seizure-induced brain damage is not conclusively demonstrated both in humans and in animal models of epilepsy. We evaluated the expression of brain injury biomarkers on post-surgical brain tissue obtained from 20 patients with frequent seizures and a long history of drug-resistant focal epilepsy. Methods The expression patterns of specific glial, neuronal and inflammatory molecules was evaluated by immunohistochemistry in the core of type II focal cortical dysplasias (FCD-II), at the FCD boundary (perilesion) and in the adjacent normal-appearing area included in the epileptogenic region...
July 27, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28748202/the-repeated-flurothyl-seizure-model-in-mice
#14
Russell J Ferland
Development of spontaneous seizures is the hallmark of human epilepsy. There is a critical need for new epilepsy models in order to elucidate mechanisms responsible for leading to the development of spontaneous seizures and for testing new anti-epileptic compounds. Moreover, rodent models of epilepsy have clearly demonstrated that there are two independent seizure systems in the brain: 1) the forebrain seizure network required for the expression of clonic seizures mediated by forebrain neurocircuitry, and 2) the brainstem seizure network necessary for the expression of brainstem or tonic seizures mediated by brainstem neurocircuitry...
June 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28746840/quantitative-assessments-of-extracellular-eeg-to-classify-specific-features-of-main-phases-of-seizure-acquisition-based-on-kindling-model-in-rat
#15
Mostafa Jalilifar, Ali Yadollahpour, Ahmad Ali Moazedi, Zohreh Ghotbeddin
OBJECTIVE: Quantitative assessments of extracellular EEG to identify specific features of three main phases of seizure acquisition based on kindling model in Rat. METHODS: Male rats were divided into 2 groups including kindled (n=10) and sham (n=7) and respectively underwent an amygdala rapid kindling and placebo kindling. EEG signals in stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage (LSS)), and 4-5 generalized seizure stages (GSSs) were divided into 5 bands: delta (0-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (12-28Hz), and gamma (28-40Hz)...
July 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28746029/early-tissue-damage-and-microstructural-reorganization-predict-disease-severity-in-experimental-epilepsy
#16
Philipp Janz, Niels Schwaderlapp, Katharina Heining, Ute Häussler, Jan G Korvink, Dominik von Elverfeldt, Jürgen Hennig, Ulrich Egert, Pierre LeVan, Carola A Haas
Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy...
July 26, 2017: ELife
https://www.readbyqxmd.com/read/28745241/the-role-of-innate-immune-system-receptors-in-epilepsy-research
#17
Oscar Arias-Carrion
Epilepsy is one of the most complex neurological disorders whose study requires a broad knowledge of neurology and neuroscience. It comprises a diverse group of neurological disorders that share the central feature of spontaneous recurrent seizures, and are often accompanied by cognitive deficits and mood disorder. This condition is one of the most common neurological disorders. Until recently, alterations of neuronal activities had been the focus of epilepsy research. This neurocentric emphasis did not address issues that arise in more complex models of epileptogenesis...
July 25, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28729934/effect-of-lamotrigine-on-seizure-development-in-a-rat-pentylenetetrazole-kindling-model
#18
Yishu Chen, Xiaokuo He, Qianqian Sun, Ziyan Fang, Liemin Zhou
INTRODUCTION: Epileptogenesis is a process of seizure development. Lamotrigine is a novel antiepileptic drug which is also used for antiepileptogenic research. Kindling models are recommended as potentially useful tools for antiepileptogenic treatment discovery. However, previous studies demonstrated that the antiepileptogenic effect of lamotrigine is controversial in the electrical kindling model. Chemical kindling such as with pentylenetetrazole is another kindling model. The aims of this study were to examine whether lamotrigine could prevent the development of seizure in pentylenetetrazole kindling rats...
July 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28729916/dynamic-expression-of-cx36-protein-in-kainic-acid-kindling-induced-epilepsy
#19
Xue-Mei Wu, Guang-Liang Wang, Xiao-Sheng Hao, Jia-Chun Feng
Connexin (Cx) 36 is known to be a component of gap junctions, and has been suggested to play an important role in epilepsy. In order to determine dynamic changes of Cx36 protein expression in epilepsy and investigate the role of Cx36 in electroencephalographic activity and pathogenesis, we utilized kainic acid (KA) to induce epileptogenesis. We found that epileptic discharges began 71.8 ± 23.7 s after KA administration. Spike frequency and amplitude of epileptiform activity reached maximal levels at 30 ± 5...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28729114/altered-intrinsic-functional-connectivity-in-the-latent-period-of-epileptogenesis-in-a-temporal-lobe-epilepsy-model
#20
Hyoin Lee, Seungmoon Jung, Peter Lee, Yong Jeong
The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition...
July 17, 2017: Experimental Neurology
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