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Epileptogenesis

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https://www.readbyqxmd.com/read/29230865/glial-source-of-nitric-oxide-in-epileptogenesis-a-target-for-disease-modification-in-epilepsy
#1
REVIEW
Shaunik Sharma, Sreekanth Puttachary, Thimmasettappa Thippeswamy
Epileptogenesis is the process of developing an epileptic condition and/or its progression once it is established. The molecules that initiate, promote, and propagate remarkable changes in the brain during epileptogenesis are emerging as targets for prevention/treatment of epilepsy. Epileptogenesis is a continuous process that follows immediately after status epilepticus (SE) in animal models of acquired temporal lobe epilepsy (TLE). Both SE and epileptogenesis are potential therapeutic targets for the discovery of anticonvulsants and antiepileptogenic or disease-modifying agents...
December 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29222951/neuronal-pas-domain-protein-4-npas4-controls-neuronal-homeostasis-in-pentylenetetrazole-induced-epilepsy-through-the-induction-of-homer1a
#2
Wei Shan, Taku Nagai, Motoki Tanaka, Norimichi Itoh, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Masahiro Sokabe, Kiyofumi Yamada
Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been implicated in epilepsy pathogenesis to prevent the neuronal circuits from hyper-excitability. Recent findings suggest a role for neuronal PAS domain protein 4 (Npas4), an activity-dependent neuron-specific transcription factor in epileptogenesis, however, the underlying mechanism by which Npas4 regulates epilepsy remains unclear. We herein propose that limbic seizure activity up-regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to epileptogenesis in mice...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29214651/electroencephalography-and-behavior-patterns-during-experimental-status-epilepticus
#3
Ewa Lewczuk, Suchitra Joshi, John Williamson, Mouna Penmetsa, Sarah Shan, Jaideep Kapur
OBJECTIVE: To characterize the evolution of behavioral and electrographic seizures in an experimental electrical stimulation-based model of status epilepticus (SE) in C57Bl/6 mice, and to relate SE to various outcomes, including death and epileptogenesis. METHODS: SE was induced by continuous hippocampal stimulation and was evaluated by review of electroencephalographic recordings, spectral display, and behavior. RESULTS: Seizures were initially locked to the electrical trains but later became independent of them...
December 6, 2017: Epilepsia
https://www.readbyqxmd.com/read/29213032/-staging-of-neuroplasticity-alterations-during-epileptogenesis-temporal-lobe-epileply-as-an-example
#4
N V Gulyaeva
Using temporal lobe epilepsy as an example, staging of long term plasticity in the hippocampus is considered. Major stages demonstrating opposite alterations in neuroplasticity are active epileptogenesis and the period of established temporal lobe epilepsy. During the epileptogenesis, multiple events resulting in forming of epileptic neuronal nets occur: changes in glutamatergic and GABAergic neurons, increase of aberrant neurogenesis, axonal sprouting and dendrite remodeling, particularly, supported by an excessive enhancement of the BDNF system in specific hippocampal regions...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29209390/the-mechanism-of-anti-epileptogenesis-by-levetiracetam-treatment-is-similar-to-the-spontaneous-recovery-of-idiopathic-generalized-epilepsy-during-adolescence
#5
Hiroki Kikuyama, Tadahito Hanaoka, Tetsufumi Kanazawa, Yasushi Yoshida, Takafumi Mizuno, Hirotaka Toyoda, Hiroshi Yoneda
Objective: The anti-epileptogenic drug levetiracetam has anticonvulsant and anti-epileptogenesis effects. Synergy between cell death and inflammation can lead to increased levels of apoptosis inhibitory factors and brain-derived neurotrophic factor, aberrant neurogenesis and extended axon sprouting. Once hyperexcitation of the neural network occurs, spontaneous seizures or epileptogenesis develops. This study investigated whether the anti-epileptogenic effect of levetiracetam is due to its alternate apoptotic activity...
November 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/29204468/dataset-of-quantitative-spectral-eeg-of-different-stages-of-kindling-acquisition-in-rats
#6
Mostafa Jalilifar, Ali Yadollahpour
The data represented here are in relation with the manuscript "Quantitative assessments of extracellular EEG to classify specific features of main phases of seizure acquisition based on kindling model in Rat" (Jalilifar et al., 2017) [1] which quantitatively classified different main stages of the kindling process based on their electrophysiological characteristics using EEG signal processing. The data in the graphical form reported the contribution of different sub bands of EEG in different stages of kindling- induced epileptogenesis...
February 2018: Data in Brief
https://www.readbyqxmd.com/read/29202749/inhibitory-or-excitatory-optogenetic-interrogation-of-the-functional-roles-of-gabaergic-interneurons-in-epileptogenesis
#7
REVIEW
Hui Ye, Stephanie Kaszuba
Alteration in the excitatory/inhibitory neuronal balance is believed to be the underlying mechanism of epileptogenesis. Based on this theory, GABAergic interneurons are regarded as the primary inhibitory neurons, whose failure of action permits hyperactivity in the epileptic circuitry. As a consequence, optogenetic excitation of GABAergic interneurons is widely used for seizure suppression. However, recent evidence argues for the context-dependent, possibly "excitatory" roles that GABAergic cells play in epileptic circuitry...
December 5, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29197620/role-of-the-fyn-pkc%C3%AE-signaling-in-se-induced-neuroinflammation-and-epileptogenesis-in-experimental-models-of-temporal-lobe-epilepsy
#8
Shaunik Sharma, Steven Carlson, Sreekanth Puttachary, Souvarish Sarkar, Lucas Showman, Marson Putra, Anumantha G Kanthasamy, Thimmasettappa Thippeswamy
Status epilepticus (SE) induces neuroinflammation and epileptogenesis, but the mechanisms are not yet fully delineated. The Fyn, a non-receptor Src family of tyrosine kinase (SFK), and its immediate downstream target, PKCδ are emerging as potential mediators of neuroinflammation. In order to first determine the role of Fyn kinase signaling in SE, we tested the efficacy of a SFK inhibitor, saracatinib (25mg/kg, oral) in C57BL/6J mouse kainate model of acute seizures. Saracatinib pretreatment dampened SE severity and completely prevented mortality...
November 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29193309/converging-early-responses-to-brain-injury-pave-the-road-to-epileptogenesis
#9
REVIEW
Eric J Neuberger, Akshay Gupta, Deepak Subramanian, Akshata A Korgaonkar, Vijayalakshmi Santhakumar
Epilepsy, characterized by recurrent seizures and abnormal electrical activity in the brain, is one of the most prevalent brain disorders. Over two million people in the United States have been diagnosed with epilepsy and 3% of the general population will be diagnosed with it at some point in their lives. While most developmental epilepsies occur due to genetic predisposition, a class of "acquired" epilepsies results from a variety of brain insults. A leading etiological factor for epilepsy that is currently on the rise is traumatic brain injury (TBI), which accounts for up to 20% of all symptomatic epilepsies...
November 29, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29193067/the-role-of-s-nitrosylation-of-kainate-type-of-ionotropic-glutamate-receptor-2-in-epilepsy-induced-by-kainic-acid
#10
Linxiao Wang, Yanyan Liu, Rulan Lu, Guoying Dong, Xia Chen, Wenwei Yun, Xianju Zhou
Epilepsy is a chronic brain disease affecting millions of individuals. Kainate receptors (KARs),especially kainate-type of ionotropic glutamate receptor 2 (GluK2), play an important role in epileptogenesis. Recent data showed GluK2 could undergo post-translational modifications in terms of S-nitrosylation (SNO), and affect the signaling pathway of cell death in cerebral ischemia-reperfusion. However, it is unclear whether S-nitrosylation of GluK2 (SNO-GluK2) contributes to cell death induced by epilepsy. Here we report that kainic acid (KA)-induced SNO-GluK2 is mediated by GluK2 itself, regulated by neuronal nitric oxide synthase (nNOS) and the level of cytoplasmic calcium in vivo and in vitro hippocampus neurons...
November 29, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29186698/effect-of-atorvastatin-on-behavioral-alterations-and-neuroinflammation-during-epileptogenesis
#11
Clarissa Vasconcelos de Oliveira, Jéssica Grigoletto, Julia Marion Canzian, Marta Maria Medeiros Frescura Duarte, Thiago Duarte, Ana Flávia Furian, Mauro Schneider Oliveira
Temporal lobe epilepsy (TLE) is the most frequent and medically refractory type of epilepsy in humans. In addition to seizures, patients with TLE suffer from behavioral alterations and cognitive deficits. Poststatus epilepticus model of TLE induced by pilocarpine in rodents has enhanced the understanding of the processes leading to epilepsy and thus, of potential targets for antiepileptogenic therapies. Clinical and experimental evidence suggests that inflammatory processes in the brain may critically contribute to epileptogenesis...
November 26, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29182639/mycophenolate-mofetil-prevents-the-delayed-t-cell-response-after-pilocarpine-induced-status-epilepticus-in-mice
#12
Anne-Marie Neumann, Julia Abele, Timo Kirschstein, Robby Engelmann, Tina Sellmann, Rüdiger Köhling, Brigitte Müller-Hilke
Growing clinical and laboratory evidence corroborates a role for the immune system in the pathophysiology of epilepsy. In order to delineate the immune response following pilocarpine-induced status epilepticus (SE) in the mouse, we monitored the kinetics of leukocyte presence in the hippocampus over the period of four weeks. SE was induced following a ramping protocol of pilocarpine injection into 4-5 weeks old C57BL/6 mice. Brains were removed at days 1-4, 14 or 28 after SE, and the hippocampi were analyzed via flow cytometry, via quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/29182533/early-gabapentin-treatment-during-the-latency-period-increases-convulsive-threshold-reduces-microglial-activation-and-macrophage-infiltration-in-the-lithium-pilocarpine-model-of-epilepsy
#13
Alicia Rossi, Veronica Murta, Jerónimo Auzmendi, Alberto Javier Ramos
The lithium-pilocarpine model of epilepsy reproduces several features of temporal lobe epilepsy in humans, including the chronological timeline of an initial latency period followed by the development of spontaneous seizures. Epilepsy therapies in humans are implemented, as a rule, after the onset of the spontaneous seizures. We here studied the potential effect on epileptogenesis of starting an early treatment during the latency period, in order to prevent the development of spontaneous seizures. Adult male Wistar rats were treated with 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine...
November 28, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29180982/resveratrol-for-easing-status-epilepticus-induced-brain-injury-inflammation-epileptogenesis-and-cognitive-and-memory-dysfunction-are-we-there-yet
#14
REVIEW
Olagide W Castro, Dinesh Upadhya, Maheedhar Kodali, Ashok K Shetty
Status epilepticus (SE) is a medical emergency exemplified by self-sustaining, unceasing seizures or swiftly recurring seizure events with no recovery between seizures. The early phase after SE event is associated with neurodegeneration, neuroinflammation, and abnormal neurogenesis in the hippocampus though the extent of these changes depends on the severity and duration of seizures. In many instances, over a period, the initial precipitating injury caused by SE leads to temporal lobe epilepsy (TLE), typified by spontaneous recurrent seizures, cognitive, memory and mood impairments associated with chronic inflammation, reduced neurogenesis, abnormal synaptic reorganization, and multiple molecular changes in the hippocampus...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29175488/influence-of-the-epileptiform-discharge-microenvironment-on-the-differentiation-of-oligodendrocyte-precursor-cells
#15
Yue Wang, Liming Liu, Hengsheng Chen, Li Cheng, Li Jiang
The use of related cell cultured models to investigate the genesis and development of epilepsy is beneficial for exploring the mechanism of epileptogenesis. Recent reports have described the myelination damage caused by epilepsy in animal models; however, limited reports have focused on the influence of epilepsy on remyelination in vitro. The current study was designed to investigate the effect of the epileptiform discharge microenvironment on the differentiation of oligodendrocyte precursor cells (OPCs). Neurons with epileptiform discharge released more glutamic acid than normal neurons, which was detected by HPLC...
November 23, 2017: Brain Research
https://www.readbyqxmd.com/read/29170537/hippocampal-mrs-and-subfield-volumetry-at-7t-detects-dysfunction-not-specific-to-seizure-focus
#16
Natalie L Voets, Carl J Hodgetts, Arjune Sen, Jane E Adcock, Uzay Emir
Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600μm isotropic resolution susceptibility-weighted images...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29168048/homozygous-expression-of-mutant-elovl4-leads-to-seizures-and-death-in-a-novel-animal-model-of-very-long-chain-fatty-acid-deficiency
#17
Blake R Hopiavuori, Ferenc Deák, Joseph L Wilkerson, Richard S Brush, Nicole A Rocha-Hopiavuori, Austin R Hopiavuori, Kathryn G Ozan, Michael T Sullivan, Jonathan D Wren, Constantin Georgescu, Luke Szweda, Vibhudutta Awasthi, Rheal Towner, David M Sherry, Robert E Anderson, Martin-Paul Agbaga
Lipids are essential components of the nervous system. However, the functions of very long-chain fatty acids (VLC-FA; ≥ 28 carbons) in the brain are unknown. The enzyme ELOngation of Very Long-chain fatty acids-4 (ELOVL4) catalyzes the rate-limiting step in the biosynthesis of VLC-FA (Agbaga et al., Proc Natl Acad Sci USA 105(35): 12843-12848, 2008; Logan et al., J Lipid Res 55(4): 698-708, 2014), which we identified in the brain as saturated fatty acids (VLC-SFA). Homozygous mutations in ELOVL4 cause severe neuropathology in humans (Ozaki et al...
November 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29153613/brain-expression-of-inflammatory-mediators-in-mesial-temporal-lobe-epilepsy-patients
#18
Bárbara Leal, João Chaves, Cláudia Carvalho, Rui Rangel, Agostinho Santos, Andreia Bettencourt, João Lopes, João Ramalheira, Berta M Silva, António Martins da Silva, Paulo P Costa
Neuroinflammation may be central in epileptogenesis. In this study we analysed inflammatory reaction markers in brain tissue of Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) patients. TLR4, IL-1β and IL-10 gene expression as well as the presence of activated HLA-DR+ microglia was evaluated in 23 patients and 10 cadaveric controls. Inflammation characterized by the presence of HLA-DR(+) microglia and TLR4, IL-1β overexpression was evident in hippocampus and anterior temporal cortex of MTLE-HS patients...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29143800/hungry-neurons-metabolic-insights-on-seizure-dynamics
#19
REVIEW
Paolo Bazzigaluppi, Azin Ebrahim Amini, Iliya Weisspapir, Bojana Stefanovic, Peter L Carlen
Epilepsy afflicts up to 1.6% of the population and the mechanisms underlying the appearance of seizures are still not understood. In past years, many efforts have been spent trying to understand the mechanisms underlying the excessive and synchronous firing of neurons. Traditionally, attention was pointed towards synaptic (dys)function and extracellular ionic species (dys)regulation. Recently, novel clinical and preclinical studies explored the role of brain metabolism (i.e., glucose utilization) of seizures pathophysiology revealing (in most cases) reduced metabolism in the inter-ictal period and increased metabolism in the seconds preceding and during the appearance of seizures...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29140112/a-2017-review-of-pharmacotherapy-for-treating-focal-epilepsy-where-are-we-now-and-how-will-treatment-develop
#20
Andreas Schulze-Bonhage
Focal epilepsy is the most common type of epilepsy with approximately 30 million patients affected worldwide. There is a major challenge to develop new antiepileptic treatments as currently approximately one third of patients remain uncontrolled under our best standards of care. Areas covered: An overview is given on first- and second generation antiepileptic drugs and their mechanisms of action, and on recent new strategies for antiepileptic targets, including drugs aiming at disease modification. Expert opinion: Newer antiepileptic drugs have enabled a better tolerated and individualized treatment for many patients...
November 15, 2017: Expert Opinion on Pharmacotherapy
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