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Epileptogenesis

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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/28508318/trpc-channels-and-epilepsy
#2
Fang Zheng
Accumulating evidence suggest that TRPC channels play critical roles in various aspects of epileptogenesis. TRPC1/4 channels are major contributors to nonsynaptically derived epileptiform burst firing in the CA1 and the lateral septum. TRPC7 channels play a critical role in synaptically derived epileptiform burst firing. The reduction of spontaneous epileptiform bursting in the CA3 is correlated to a reduction in pilocarpine-induced SE in vivo in TRPC7 knockout mice. TRPC channels are also significant contributors to SE-induced neuronal cell death...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28508204/rearing-by-foster-wistar-mother-with-high-level-of-maternal-care-counteracts-the-development-of-genetic-absence-epilepsy-and-comorbid-depression-in-wag-rij-rats
#3
K Yu Sarkisova, A V Gabova, M A Kulikov, E A Fedosova, A B Shatskova, A A Morosov
It has been shown for the first time that rearing by a foster Wistar mother with high level of maternal care (MC) counteracts the expression of genetic absence epilepsy (AE) and comorbid depression - reduces the number, duration and index of spike-wave discharges (SWDs) and immobility time in the forced swimming test, as well as exerts substantial effects on morphology and time-frequency dynamics of SWDs in WAG/Rij rats. It is supposed that increases in MC early in development might be used to counteract epileptogenesis and comorbid depression in people genetically predisposed to AE...
March 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28504645/molecular-isoforms-of-high-mobility-group-box-1-are-mechanistic-biomarkers-for-epilepsy
#4
Lauren Elizabeth Walker, Federica Frigerio, Teresa Ravizza, Emanuele Ricci, Karen Tse, Rosalind E Jenkins, Graeme John Sills, Andrea Jorgensen, Luca Porcu, Thimmasettappa Thippeswamy, Tiina Alapirtti, Jukka Peltola, Martin J Brodie, Brian Kevin Park, Anthony Guy Marson, Daniel James Antoine, Annamaria Vezzani, Munir Pirmohamed
Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28494616/breakdown-of-thalamo-cortical-connectivity-precedes-spike-generation-in-focal-epilepsies
#5
Vitalie Chiosa, Stanislav Alexandru Groppa, Dimitru Ciolac, Nabin Koirala, Liuda Misina, Yaroslav Winter, Maria Moldovanu, Muthuraman Muthuraman, Sergiu Groppa
EEG spikes and focal epileptic seizures are generated in circumscribed cerebral networks that have been insufficiently described. For precise time and spatial domain networks characterization we applied in patients with focal epilepsy dense array 256-channel EEG recordings with causal connectivity estimation using time resolved partial directed coherence and 3T-MRI derived cortical and thalamus integrity reconstruction. Prior to spike generation significant theta and alpha bands driven information flows alterations were noted from both temporal and frontal lobes to thalamus and from thalamus to the frontal lobe...
May 11, 2017: Brain Connectivity
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
#6
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/28487411/a-microrna-129-5p-rbfox-crosstalk-coordinates-homeostatic-downscaling-of-excitatory-synapses
#7
Marek Rajman, Franziska Metge, Roberto Fiore, Sharof Khudayberdiev, Ayla Aksoy-Aksel, Silvia Bicker, Cristina Ruedell Reschke, Rana Raoof, Gary P Brennan, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Sebastian Bauer, Braxton Norwood, Morten T Veno, Marcus Krüger, Thomas Braun, Jørgen Kjems, Felix Rosenow, David C Henshall, Christoph Dieterich, Gerhard Schratt
Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)-treated hippocampal neurons, a model of synaptic downscaling. Thereby, we identified eight microRNAs (miRNAs) that were increased in response to PTX, including miR-129-5p, whose inhibition blocked synaptic downscaling in vitro and reduced epileptic seizure severity in vivo Using transcriptome, proteome, and bioinformatic analysis, we identified the calcium pump Atp2b4 and doublecortin (Dcx) as miR-129-5p targets...
May 9, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28486943/kb-r7943-reduces-4-aminopyridine-induced-epileptiform-activity-in-adult-rats-after-neuronal-damage-induced-by-neonatal-monosodium-glutamate-treatment
#8
Mariana Hernandez-Ojeda, Monica E Ureña-Guerrero, Paola E Gutierrez-Barajas, Jazmin A Cardenas-Castillo, Antoni Camins, Carlos Beas-Zarate
BACKGROUND: Neonatal monosodium glutamate (MSG) treatment triggers excitotoxicity and induces a degenerative process that affects several brain regions in a way that could lead to epileptogenesis. Na(+)/Ca(2+) exchangers (NCX1-3) are implicated in Ca(2+) brain homeostasis; normally, they extrude Ca(2+) to control cell inflammation, but after damage and in epilepsy, they introduce Ca(2+) by acting in the reverse mode, amplifying the damage. Changes in NCX3 expression in the hippocampus have been reported immediately after neonatal MSG treatment...
May 9, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28473263/differences-in-white-matter-structure-between-seizure-prone-fast-and-seizure-resistant-slow-rat-strains
#9
Pragati Sharma, David K Wright, Leigh A Johnston, Kim L Powell, Mary E Wlodek, Sandy R Shultz, Terence J O'Brien, Krista L Gilby
Alterations in white matter integrity have been well documented in chronic epilepsy and during epileptogenesis. However, the relationship between white matter integrity and a predisposition towards epileptogenesis has been understudied. The FAST rat strain exhibit heightened susceptibility towards kindling epileptogenesis whereas SLOW rats are highly resistant. FAST rats also display behavioral phenotypes reminiscent of those observed in neurodevelopmental disorders that commonly comorbid with epilepsy. In this study, we aim to identify differences in white matter integrity that may contribute to a predisposition towards epileptogenesis and its associated comorbidities in 6month old FAST (n=10) and SLOW (n=10) male rats...
May 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28470680/rabies-tracing-of-birthdated-dentate-granule-cells-in-rat-temporal-lobe-epilepsy
#10
Xi Du, Helen Zhang, Jack M Parent
OBJECTIVE: To understand how monosynaptic inputs onto adult-born dentate granule cells (DGCs) are altered in experimental mesial temporal lobe epilepsy (mTLE) and whether their integration differs from early-born DGCs that are mature at the time of epileptogenesis. METHODS: A dual-virus tracing strategy combining retroviral birthdating with rabies virus-mediated putative retrograde trans-synaptic tracing was used to identify and compare presynaptic inputs onto adult- and early-born DGCs in the rat pilocarpine model of mTLE...
May 3, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28468530/the-epigenetics-of-epilepsy-and-its-progression
#11
Rebecca M Hauser, David C Henshall, Farah D Lubin
Epilepsy is a common and devastating neurological disorder characterized by recurrent and unprovoked spontaneous seizures. One leading hypothesis for the development and progression of epilepsy is that large-scale changes in gene transcription and protein expression contribute to aberrant network restructuring and hyperexcitability, resulting in the genesis of repeated seizures. Current research shows that epigenetic mechanisms, including posttranslational alterations to the proteins around which DNA is coiled, chemical modifications to DNA, and the activity of various noncoding RNA molecules exert important influences on these gene networks in experimental epilepsy...
May 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28462087/identification-of-brain-regions-predicting-epileptogenesis-by-serial-18-f-ge-180-positron-emission-tomography-imaging-of-neuroinflammation-in-a-rat-model-of-temporal-lobe-epilepsy
#12
Vera Russmann, Matthias Brendel, Erik Mille, Angela Helm-Vicidomini, Roswitha Beck, Lisa Günther, Simon Lindner, Axel Rominger, Michael Keck, Josephine D Salvamoser, Nathalie L Albert, Peter Bartenstein, Heidrun Potschka
Excessive activation of inflammatory signaling pathways seems to be a hallmark of epileptogenesis. Positron emission tomography (PET) allows in vivo detection of brain inflammation with spatial information and opportunities for longitudinal follow-up scanning protocols. Here, we assessed whether molecular imaging of the 18 kDa translocator protein (TSPO) can serve as a biomarker for the development of epilepsy. Therefore, brain uptake of [(18)F]GE-180, a highly selective radioligand of TSPO, was investigated in a longitudinal PET study in a chronic rat model of temporal lobe epilepsy...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28455787/elevated-expression-of-trpc4-in-cortical-lesions-of-focal-cortical-dysplasia-ii-and-tuberous-sclerosis-complex
#13
Lu-Kang Wang, Xin Chen, Chun-Qing Zhang, Chao Liang, Yu-Jia Wei, Jiong Yue, Shi-Yong Liu, Hui Yang
Focal cortical dysplasia type II (FCD II) and tuberous sclerosis complex (TSC) are well-known causes of chronic refractory epilepsy in children. Canonical transient receptor potential channels (TRPCs) are non-selective cation channels that are commonly activated by phospholipase C (PLC) stimulation. Previous studies found that TRPC4 may participate in the process of epileptogenesis. This study aimed to examine the expression and distribution of TRPC4 in FCD II (n = 24) and TSC (n = 11) surgical specimens compared with that in age-matched autopsy control samples (n = 12)...
April 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28452419/neurosteroid-sensitive-%C3%AE-gabaa-receptors-a-role-in-epileptogenesis
#14
Suchitra Joshi, Karthik Rajasekaran, John Williamson, Jaideep Kapur
OBJECTIVE: We determined the role of the neurosteroid-sensitive δ subunit-containing γ-aminobutyric acid A receptors (δ-GABARs) in epileptogenesis. METHODS: Status epilepticus (SE) was induced via lithium pilocarpine in adult rats, and seizures were assessed by continuous video-electroencephalography (EEG) monitoring. Finasteride was administered to inhibit neurosteroid synthesis. The total and surface protein expression of hippocampal δ, α4, and γ2 GABAR subunits was studied using biotinylation assays and Western blotting...
March 2017: Epilepsia
https://www.readbyqxmd.com/read/28444637/phase-dependent-astroglial-alterations-in-li-pilocarpine-induced-status-epilepticus-in-young-rats
#15
Adriana Fernanda K Vizuete, Matheus Mittmann Hennemann, Carlos Alberto Gonçalves, Diogo Losch de Oliveira
Epilepsy prevalence is high in infancy and in the elderly population. Lithium-pilocarpine is widely used to induce experimental animal models of epilepsy, leading to similar neurochemical and morphological alterations to those observed in temporal lobe epilepsy. As astrocytes have been implicated in epileptic disorders, we hypothesized that specific astroglial changes accompany and contribute to epileptogenesis. Herein, we evaluated time-dependent astroglial alterations in the hippocampus of young (27-day-old) rats at 1, 14 and 56 days after Li-pilocarpine-induced status epilepticus (SE), corresponding to different phases in this model of epilepsy...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28444141/imaging-blood-brain-barrier-dysfunction-as-a-biomarker-for-epileptogenesis
#16
Guy Bar-Klein, Svetlana Lublinsky, Lyn Kamintsky, Iris Noyman, Ronel Veksler, Hotjensa Dalipaj, Vladimir V Senatorov, Evyatar Swissa, Dror Rosenbach, Netta Elazary, Dan Z Milikovsky, Nadav Milk, Michael Kassirer, Yossi Rosman, Yonatan Serlin, Arik Eisenkraft, Yoash Chassidim, Yisrael Parmet, Daniela Kaufer, Alon Friedman
A biomarker that will enable the identification of patients at high-risk for developing post-injury epilepsy is critically required. Microvascular pathology and related blood-brain barrier dysfunction and neuroinflammation were shown to be associated with epileptogenesis after injury. Here we used prospective, longitudinal magnetic resonance imaging to quantitatively follow blood-brain barrier pathology in rats following status epilepticus, late electrocorticography to identify epileptic animals and post-mortem immunohistochemistry to confirm blood-brain barrier dysfunction and neuroinflammation...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28441631/up-regulated-baff-and-baff-receptor-expression-in-patients-with-intractable-temporal-lobe-epilepsy-and-a-pilocarpine-induced-epilepsy-rat-model
#17
Limin Ma, Ruohan Li, Hao Huang, Jinxian Yuan, Shu Ou, Tao Xu, Xinyuan Yu, Xi Liu, Yangmei Chen
PURPOSE: Some studies have suggested that BAFF and BAFFR are highly expressed in the central nervous system (CNS) and participate in inflammatory and immune associated diseases. However, whether BAFF and BAFFR are involved in the pathogenesis of epilepsy remains unknown. This study aimed to investigate the expression of BAFF and BAFFR proteins in the brains of patients with temporal lobe epilepsy (TLE) and in a pilocarpine-induced rat model of TLE to identify possible roles of the BAFF-BAFFR signaling pathway in epileptogenesis...
April 8, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28438505/turning-down-the-volume-astrocyte-volume-change-in-the-generation-and-termination-of-epileptic-seizures
#18
REVIEW
Thomas R Murphy, Devin K Binder, Todd A Fiacco
Approximately 1% of the global population suffers from epilepsy, a class of disorders characterized by recurrent and unpredictable seizures. Of these cases roughly one-third are refractory to current antiepileptic drugs, which typically target neuronal excitability directly. The events leading to seizure generation and epileptogenesis remain largely unknown, hindering development of new treatments. Some recent experimental models of epilepsy have provided compelling evidence that glial cells, especially astrocytes, could be central to seizure development...
April 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28438504/agomelatine-protects-against-neuronal-damage-without-preventing-epileptogenesis-in-the-kainate-model-of-temporal-lobe-epilepsy
#19
Jana Tchekalarova, Dimitrinka Atanasova, Zlatina Nenchovska, Milena Atanasova, Lidia Kortenska, Rumyana Gesheva, Nikolai Lazarov
Recent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE)...
April 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28436627/-temporal-lobe-epilepsy-and-adult-hippocampal-neurogenesis
#20
Liying Chen, Yi Wang, Zhong Chen
Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE)...
January 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
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