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animal model of temporal lobe epilepsy

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https://www.readbyqxmd.com/read/29367144/a-clinical-grade-gene-therapy-vector-for-pharmacoresistant-epilepsy-successfully-overexpresses-npy-in-a-human-neuronal-cell-line
#1
Maria I Patrício, Alun R Barnard, Alexander L Green, Matthew J During, Arjune Sen, Robert E MacLaren
PURPOSE: Epilepsy is a common neurological condition characterised by recurrent unprovoked seizures and often treatable with appropriate medication. However, almost 30% of cases are pharmacoresistant and while a proportion of these may be amenable to resective surgery, a gene therapy approach could be an attractive alternative option. Neuropeptide Y (NPY) has anticonvulsant and anti-epileptogenic properties in animal models of temporal lobe epilepsy when delivered by an adeno-associated viral (AAV) vector...
December 18, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29364511/-18-f-ge180-positron-emission-tomographic-imaging-indicates-a-potential-double-hit-insult-in-the-intrahippocampal-kainate-mouse-model-of-temporal-lobe-epilepsy
#2
Mirjam Brackhan, Pablo Bascuñana, Tobias L Ross, Frank M Bengel, Jens P Bankstahl, Marion Bankstahl
OBJECTIVE: Accumulating evidence suggests that brain inflammation, elicited by epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear imaging of brain inflammation in animal models of epileptogenesis represents a diagnostic in vivo approach with potential for direct translation into the clinic. Here, we investigated up-regulation of the translocator protein (TSPO) indicative of microglial activation by serial [18 F]GE180 positron emission tomographic (PET) imaging in a mouse model of temporal lobe epilepsy...
January 24, 2018: Epilepsia
https://www.readbyqxmd.com/read/29303444/reductions-in-brain-pericytes-are-associated-with-arteriovenous-malformation-vascular-instability
#3
Ethan A Winkler, Harjus Birk, Jan-Karl Burkhardt, Xiaolin Chen, John K Yue, Diana Guo, W Caleb Rutledge, George F Lasker, Carlene Partow, Tarik Tihan, Edward F Chang, Hua Su, Helen Kim, Brian P Walcott, Michael T Lawton
OBJECTIVE Brain arteriovenous malformations (bAVMs) are rupture-prone tangles of blood vessels with direct shunting of blood flow between arterial and venous circulations. The molecular and/or cellular mechanisms contributing to bAVM pathogenesis and/or destabilization in sporadic lesions have remained elusive. Initial insights into AVM formation have been gained through models of genetic AVM syndromes. And while many studies have focused on endothelial cells, the contributions of other vascular cell types have yet to be systematically studied...
January 5, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29282779/dynamics-underlying-interictal-to-ictal-transition-in-temporal-lobe-epilepsy-insights-from-a-neural-mass-model
#4
Xiaoya Fan, Nicolas Gaspard, Benjamin Legros, Federico Lucchetti, Rudy Ercek, Antoine Nonclercq
We propose an approach that combines a neural mass model and clinical intracranial electroencephalographic (iEEG) recordings to explore the potential pathophysiological mechanisms (at the neuronal population level) of ictogenesis. Thirty iEEG recordings from ten temporal lobe epilepsy (TLE) patients around seizure onset were investigated. Physiologically meaningful parameters (average excitatory [Ae], slow [B] and fast [G] inhibitory synaptic gain) were identified during interictal to ictal transition. Four ratios (Ae/G, Ae/B, Ae/(B+G) and B/G) were derived from these parameters and their evolution over time were analyzed...
December 28, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29273763/interactions-between-ghrh-and-gabaars-in-the-brains-of-patients-with-epilepsy-and-in-animal-models-of-epilepsy
#5
Shirong Tang, Zhong Luo, Xiaowei Qiu, Yanke Zhang, Xi Lu, Hao Huang, Zhongxiang Xu, Zucai Xu
Growth hormone releasing hormone (GHRH) has recently been shown to increase the level of γ-aminobutyric acid (GABA) and activate GABA receptors (GABARs) in the cerebral cortex. GABA is an inhibitory neurotransmitter that can inhibit seizures. Does GHRH enhance the inhibitory effect of GABA to prevent epilepsy by increasing the GABA level and activating GABARs? In this study, patients with epilepsy and C57/BL6 mice with epilepsy induced by kainic acid (KA) or pentylenetetrazol (PTZ) served as the research subjects...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29247482/commonalities-in-epileptogenic-processes-from-different-acute-brain-insults-do-they-translate
#6
REVIEW
Pavel Klein, Raymond Dingledine, Eleonora Aronica, Christophe Bernard, Ingmar Blümcke, Detlev Boison, Martin J Brodie, Amy R Brooks-Kayal, Jerome Engel, Patrick A Forcelli, Lawrence J Hirsch, Rafal M Kaminski, Henrik Klitgaard, Katja Kobow, Daniel H Lowenstein, Phillip L Pearl, Asla Pitkänen, Noora Puhakka, Michael A Rogawski, Dieter Schmidt, Matti Sillanpää, Robert S Sloviter, Christian Steinhäuser, Annamaria Vezzani, Matthew C Walker, Wolfgang Löscher
The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification...
December 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/29237452/molecular-cloning-and-characterization-of-the-family-of-feline-leucine-rich-glioma-inactivated-lgi-genes-and-mutational-analysis-in-familial-spontaneous-epileptic-cats
#7
Yoshihiko Yu, Daisuke Hasegawa, Aki Fujiwara-Igarashi, Yuji Hamamoto, Shunta Mizoguchi, Takayuki Kuwabara, Michio Fujita
BACKGROUND: Leucine-rich glioma-inactivated (LGI) proteins play a critical role in synaptic transmission. Dysfunction of these genes and encoded proteins is associated with neurological disorders such as genetic epilepsy or autoimmune limbic encephalitis in animals and human. Familial spontaneous epileptic cats (FSECs) are the only feline strain and animal model of familial temporal lobe epilepsy. The seizure semiology of FSECs comprises recurrent limbic seizures with or without evolution into generalized epileptic seizures, while cats with antibodies against voltage-gated potassium channel complexed/LGI1 show limbic encephalitis and recurrent limbic seizures...
December 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29230865/glial-source-of-nitric-oxide-in-epileptogenesis-a-target-for-disease-modification-in-epilepsy
#8
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/29209207/antiepileptic-and-neuroprotective-effects-of-oleamide-in-rat-striatum-on-kainate-induced-behavioral-seizure-and-excitotoxic-damage-via-calpain-inhibition
#9
Hye Yeon Nam, Eun Jung Na, Eunyoung Lee, Youngjoo Kwon, Hwa-Jung Kim
Oleamide was first known as a sleep-inducing fatty acid amide, and later shown to have wide range of neuropharmacological effects upon different neurochemical systems. However, the effects of oleamide on brain damage have scarcely been studied, and the molecular mechanisms and sites of its action remain elusive. Kainic acid (KA) has been used to produce an epileptic animal model that mimics human temporal lobe epilepsy and to induce calpain-activated excitotoxicity, which occurs in numerous neurodegenerative disorders...
2017: Frontiers in Pharmacology
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
#10
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/29182533/early-gabapentin-treatment-during-the-latency-period-increases-convulsive-threshold-reduces-microglial-activation-and-macrophage-infiltration-in-the-lithium-pilocarpine-model-of-epilepsy
#11
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/29163349/kainic-acid-induced-post-status-epilepticus-models-of-temporal-lobe-epilepsy-with-diverging-seizure-phenotype-and-neuropathology
#12
Daniele Bertoglio, Halima Amhaoul, Annemie Van Eetveldt, Ruben Houbrechts, Sebastiaan Van De Vijver, Idrish Ali, Stefanie Dedeurwaerdere
The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29130506/animal-models-of-acquired-epilepsy-insights-into-mechanisms-of-human-epileptogenesis
#13
Albert J Becker
In many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias (FCDs) and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, i...
November 12, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29111385/jnk1-inhibition-by-licochalcone-a-leads-to-neuronal-protection-against-excitotoxic-insults-derived-of-kainic-acid
#14
Oriol Busquets, Miren Ettcheto, Ester Verdaguer, Rubén Dario, Carme Auladell, Carlos Beas-Zarate, Jaume Folch, Antoni Camins
The mitogen-activated protein kinase family (MAPK) is an important group of enzymes involved in cellular responses to diverse external stimuli. One of the members of this family is the c-Jun-N-terminal kinase (JNK). The activation of the JNK pathway has been largely associated with the pathogenesis that occurs in epilepsy and neurodegeneration. Kainic acid (KA) administration in rodents is an experimental approach that induces status epilepticus (SE) and replicates many of the phenomenological features of human temporal lobe epilepsy (TLE)...
October 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29101217/epigenetic-histone-deacetylation-inhibition-prevents-the-development-and-persistence-of-temporal-lobe-epilepsy
#15
Sandesh D Reddy, Bryan C Clossen, Doodipala Samba Reddy
Epilepsy is a chronic brain disease characterized by repeated unprovoked seizures. Currently, no drug therapy exists for curing epilepsy or disease-modification in people at risk. Despite several emerging mechanisms, there have been few studies of epigenetic signaling in epileptogenesis, the process whereby a normal brain becomes progressively epileptic because of precipitating factors. Here, we report a novel role of histone deacetylation as critical epigenetic mechanism in epileptogenesis. Experiments were conducted using the histone deacetylase (HDAC) inhibitor sodium butyrate in the hippocampus kindling model of temporal lobe epilepsy (TLE), a classic model heavily used to approve drugs for treatment of epilepsy...
November 3, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29093637/structural-and-functional-alterations-at-pre-epileptic-stage-are-closely-associated-with-epileptogenesis-in-pilocarpine-induced-epilepsy-model
#16
Hani Kim, Yunsook Choi, Hye-Young Joung, Yun Seo Choi, Hyeon Jin Kim, Yohan Joo, Jin-Hwan Oh, Hoo Jae Hann, Zang-Hee Cho, Hyang Woon Lee
Pilocarpine-induced rat epilepsy model is an established animal model that mimics medial temporal lobe epilepsy in humans. The purpose of this study was to investigate neuroimaging abnormalities in various stages of epileptogenesis and to correlate them with seizure severity in pilocarpine-induced rat epilepsy model. Fifty male Sprague-Dawley rats were subject to continuous video and electroencephalographic monitoring after inducing status epilepticus (SE) and seizure severity was estimated by frequency and total durations of class 3 to 5 spontaneous recurrent seizures (SRS) by modified Racine's classification...
October 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29088985/anticonvulsant-effect-of-gentamicin-on-the-seizures-induced-by-kainic-acid
#17
Yuxiao Zhao, Ziyi Wang, Wenwen Lao, Ping Kuang, Nan Jiang, Tao Yin, Weide Lin, Hongyan Zhu, Yonghua Ji
OBJECTIVE:  Epilepsy is a chronic neurological disorder affecting approximately 0.5-2% of the population worldwide. Gentamicin (GM) is an aminoglycoside antibiotic used to treat several types of bacterial infections. We investigate whether the administration of GM can reduce seizures in temporal lobe epilepsy (TLE). METHODS: The animal model of temporal lobe epilepsy (TLE) was established by kainic acid (KA) intrahippocampal injection. Behavioral test and Electroencephalography (EEG) recordings were performed to detect the effects of GM on the seizures triggered by KA injection in rats...
October 31, 2017: Neurological Research
https://www.readbyqxmd.com/read/29070854/altered-norbin-expression-in-patients-with-epilepsy-and-a-rat-model
#18
Yali Xu, Zengyou Li, Li Yao, Xingping Zhang, Dan Gan, Manchun Jiang, Na Wang, Guojun Chen, Xuefeng Wang
Norbin is widely distributed in neuronal tissues, is a regulator of Ca2(+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation. Norbin is also an important endogenous modulator of metabotropic glutamate receptor 5 (mGluR5) signaling, and nervous system-specific homozygous gene disruptions, result in epileptic seizures. In this study, we aimed to investigate norbin expression patterns in epilepsy and to elucidate the relationships between norbin and mGluR5 and p-CaMKII in epilepsy. Double-immunolabeling, immunohistochemistry and immunoblotting studies showed that norbin was downregulated in the temporal neocortex of patients with temporal lobe epilepsy (TLE) compared with control subjects...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29069823/microrna-134-plasma-levels-before-and-after-treatment-with-valproic-acid-for-epilepsy-patients
#19
Xiaofeng Wang, Yifeng Luo, Shuangxi Liu, Liming Tan, Sanhu Wang, Rongyong Man
BACKGROUND: Temporal lobe epilepsy is the second most common neurological disorders characterized by recurrent spontaneous seizures. MicroRNAs play a vital role in regulating synaptic plasticity, brain development and post-transcriptional expression of proteins. In both animal models of epilepsy and human patients, miR-134, a brain-specific microRNA has recently been identified as a potential regulator of epileptogenesis. METHODS: microRNA identified as targets for the actions of valproic acid (VPA) are known to have important effects in brain function...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29060316/a-machine-learning-approach-to-characterizing-the-effect-of-asynchronous-distributed-electrical-stimulation-on-hippocampal-neural-dynamics-in-vivo
#20
Mark J Connolly, Sang-Eon Park, Robert E Gross, Babak Mahmoudi
Asynchronous distributed microelectrode theta stimulation (ADMETS) of the hippocampus has been shown to reduce seizure frequency in the tetanus toxin rat model of mesial temporal lobe epilepsy suggesting a hypothesis that ADMETS induces a seizure resistant state. Here we present a machine learning approach to characterize the nature of neural state changes induced by distributed stimulation. We applied the stimulation to two animals under sham and ADMETS conditions and used a combination of machine learning techniques on intra-hippocampal recordings of Local Field Potentials (LFPs) to characterize the difference in the neural state between sham and ADMETS...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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