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Amygdala kindling

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https://www.readbyqxmd.com/read/29881810/facilitation-of-kindling-epileptogenesis-by-chronic-stress-may-be-mediated-by-intestinal-microbiome
#1
Jesús-Servando Medel-Matus, Don Shin, Edward Dorfman, Raman Sankar, Andrey Mazarati
There has been growing interest in the role of intestinal microbiome in brain disorders. We examined whether dysbiosis can predispose to epilepsy. The study was performed in female and male Sprague-Dawley rats. To induce dysbiosis, the rats were subjected to chronic restraint stress (two 2-h long sessions per day, over 2 weeks). Cecal content from stressed and sham-stressed donors was transplanted via oral gavage to recipients, in which commensal microbiota had been depleted by the antibiotics. The study included the following groups: (1) Sham stress, no microbiota transplant; (2) Stress, no microbiota transplant; (3) Sham-stressed recipients transplanted with microbiota from sham-stressed donors; (4) Stressed recipients transplanted with microbiota from sham-stressed donors; (5) Sham-stressed recipients transplanted with microbiota from stressed donors; and (6) Stressed recipients transplanted with microbiota from stressed donors...
June 2018: Epilepsia open
https://www.readbyqxmd.com/read/29858497/chronic-fluoxetine-treatment-accelerates-kindling-epileptogenesis-in-mice-independently-of-5-ht-2a-receptors
#2
Crystal Li, Juliana Silva, Ezgi Ozturk, Gabriella Dezsi, Terence J O'Brien, Thibault Renoir, Nigel C Jones
Patients with epilepsy often have mood disorders, and these are commonly treated with antidepressant drugs. Although these drugs are often successful in mitigating depressive symptoms, how they affect the epileptogenic processes has been little studied. Recent evidence has demonstrated that treatment with selective serotonin reuptake inhibitor (SSRI) antidepressant drugs adversely promotes epileptogenesis, which may be of great concern considering the number of patients exposed to these drugs. This study investigated 5-HT2A receptor signaling as a potential mechanism driving the pro-epileptogenic effects of the prototypical SSRI fluoxetine...
June 1, 2018: Epilepsia
https://www.readbyqxmd.com/read/29787768/the-angiotensin-ii-type-i-receptor-antagonist-losartan-retards-amygdala-kindling-induced-epileptogenesis
#3
Toshiki Nozaki, Hiroyuki Ura, Ichiro Takumi, Shiro Kobayashi, Eiichi Maru, Akio Morita
Blood-brain barrier (BBB) breakdown and the subsequent exposure of the cerebral cortex to serum albumin are known to activate transforming growth factor β (TGF- β) signaling in astrocytes and to play key roles in epileptogenesis after brain injury. It was recently reported that the angiotensin II type I receptor antagonist losartan suppresses activation of TGF- β signaling and prevents epileptogenesis in a rat vascular injury model. Here, we investigated the effects of losartan on epileptogenesis following amygdala kindling in rats...
May 19, 2018: Brain Research
https://www.readbyqxmd.com/read/29778948/bioisosteres-of-ethyl-8-ethynyl-6-pyridin-2-yl-4h-benzo-f-imidazo-1-5-a-1-4-diazepine-3-carboxylate-hz-166-as-novel-alpha-2-3-selective-potentiators-of-gaba-a-receptors-improved-bioavailability-enhances-anticonvulsant-efficacy
#4
J M Witkin, J L Smith, X Ping, S D Gleason, M M Poe, G Li, X Jin, J Hobbs, J M Schkeryantz, J S McDermott, A I Alatorre, J N Siemian, J W Cramer, D C Airey, K R Methuku, V V N P B Tiruveedhula, T M Jones, J Crawford, M J Krambis, J L Fisher, J M Cook, R Cerne
HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29750337/lamotrigine-resistant-corneal-kindled-mice-a-model-of-pharmacoresistant-partial-epilepsy-for-moderate-throughput-drug-discovery
#5
Zachery Koneval, Kevin M Knox, H Steve White, Melissa Barker-Haliski
OBJECTIVE: Despite numerous treatments for epilepsy, over 30% of patients remain resistant to available antiseizure drugs (ASDs). Thus, there is a strong need for more effective ASDs for these individuals. Early ASD discovery has historically relied on acute in vivo seizure models (maximal electroshock, subcutaneous pentylenetetrazol, 6 Hz), which lack the pathophysiology that defines chronic epilepsy. Etiologically relevant rodent models of pharmacoresistant epilepsy exist (eg, phenytoin (PHT)- and lamotrigine (LTG)-resistant amygdala-kindled rat and focal kainic acid mouse), but these models are resource- and labor-intensive and thus unsuitable for frontline ASD discovery...
May 11, 2018: Epilepsia
https://www.readbyqxmd.com/read/29663353/positron-emission-tomography-imaging-of-cerebral-glucose-metabolism-and-type-1-cannabinoid-receptor-availability-during-temporal-lobe-epileptogenesis-in-the-amygdala-kindling-model-in-rhesus-monkeys
#6
Evy Cleeren, Cindy Casteels, Karolien Goffin, Michel Koole, Koen Van Laere, Peter Janssen, Wim Van Paesschen
OBJECTIVE: We investigated changes in the endocannabinoid system and glucose metabolism during temporal lobe epileptogenesis. METHODS: Because it is rarely possible to study epileptogenesis in humans, we applied the electrical amygdala kindling model in nonhuman primates to image longitudinal changes in type 1 cannabinoid receptor (CB1R) binding and cerebral glucose metabolism. Two rhesus monkeys received [18 F]-MK-9470 and fluorodeoxyglucose-positron emission tomography ([18 F]-FDG -PET) scans in each of the 4 kindling stages to quantify relative changes over time of CB1R binding and cerebral glucose metabolism in vivo...
May 2018: Epilepsia
https://www.readbyqxmd.com/read/29346088/intense-olfactory-stimulation-blocks-seizures-in-an-experimental-model-of-epilepsy
#7
Polianna Delfino-Pereira, Poliana Bertti-Dutra, Eduardo Henrique de Lima Umeoka, José Antônio Cortes de Oliveira, Victor Rodrigues Santos, Artur Fernandes, Simone Saldanha Marroni, Flávio Del Vecchio, Norberto Garcia-Cairasco
There are reports of patients whose epileptic seizures are prevented by means of olfactory stimulation. Similar findings were described in animal models of epilepsy, such as the electrical kindling of amygdala, where olfactory stimulation with toluene (TOL) suppressed seizures in most rats, even when the stimuli were 20% above the threshold to evoke seizures in already kindled animals. The Wistar Audiogenic Rat (WAR) strain is a model of tonic-clonic seizures induced by acute acoustic stimulation, although it also expresses limbic seizures when repeated acoustic stimulation occurs - a process known as audiogenic kindling (AK)...
February 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29317669/selective-targeting-of-scn8a-prevents-seizure-development-in-a-mouse-model-of-mesial-temporal-lobe-epilepsy
#8
Jennifer C Wong, Christopher D Makinson, Tyra Lamar, Qi Cheng, Jeffrey C Wingard, Ernest F Terwilliger, Andrew Escayg
We previously found that genetic mutants with reduced expression or activity of Scn8a are resistant to induced seizures and that co-segregation of a mutant Scn8a allele can increase survival and seizure resistance of Scn1a mutant mice. In contrast, Scn8a expression is increased in the hippocampus following status epilepticus and amygdala kindling. These findings point to Scn8a as a promising therapeutic target for epilepsy and raise the possibility that aberrant overexpression of Scn8a in limbic structures may contribute to some epilepsies, including temporal lobe epilepsy...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29114861/kappa-opioid-receptors-regulate-hippocampal-synaptic-homeostasis-and-epileptogenesis
#9
Bridget N Queenan, Raymond L Dunn, Victor R Santos, Yang Feng, Megan N Huizenga, Robert J Hammack, Stefano Vicini, Patrick A Forcelli, Daniel T S Pak
OBJECTIVE: Homeostatic synaptic plasticity (HSP) serves as a gain control mechanism at central nervous system (CNS) synapses, including those between the dentate gyrus (DG) and CA3. Improper circuit control of DG-CA3 synapses is hypothesized to underlie epileptogenesis. Here, we sought to (1) identify compounds that preferentially modulate DG-CA3 synapses in primary neuronal culture and (2) determine if these compounds would delay or prevent epileptogenesis in vivo. METHODS: We previously developed and validated an in vitro assay to visualize the behavior of DG-CA3 synapses and predict functional changes...
January 2018: Epilepsia
https://www.readbyqxmd.com/read/29107199/kindling-epileptogenesis-and-panic-like-behavior-their-bidirectional-connection-and-contribution-to-epilepsy-associated-depression
#10
Jesús-Servando Medel-Matus, Don Shin, Raman Sankar, Andrey Mazarati
Anxiety is one of the most common comorbidities of epilepsy, which has major detrimental effects on the quality of life. Generalized anxiety disorder (GAD) associated with epilepsy has been receiving most attention. However, several other forms of anxiety reportedly present in patients with epilepsy, including panic disorder (PD). In this study, using an animal model of limbic epilepsy, we examined the interplay between epilepsy and panic-like behavior (PLB). Further, considering the high degree of comorbidity between depression on the one hand, and both epilepsy and PD on the other hand, we studied whether and how the presence of PLB in animals with epilepsy would affect their performance in depression-relevant tests...
December 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29090671/targeted-blockade-of-tarp-%C3%AE-8-associated-ampa-receptors-anticonvulsant-activity-with-the-selective-antagonist-ly3130481-cerc-611
#11
Jeffrey M Witkin, Douglas A Schober, Scott D Gleason, John T Catlow, Warren J Porter, Jon Reel, Xiaoming Jin, Jonathan Hobbs, Donald Gehlert, Douglas L Gernert, Kevin M Gardinier, Akihiko S Kato, Xingjie Ping, Jodi L Smith
BACKGROUND & OBJECTIVE: 6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]- 3H-1,3-benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA receptors containing transmembrane AMPA receptor regulatory protein (TARP) γ-8 that is under development for epilepsy. The present study provided a broad inquiry into its anticonvulsant properties. LY3130481 was anticonvulsant in multiple acute seizure provocation models in mice and rats. In addition, LY3130481 was effective against absence seizures in the GAERS genetic model and in the Frings mouse model...
2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28948088/linking-kindling-to-increased-glutamate-release-in-the-dentate-gyrus-of-the-hippocampus-through-the-stxbp5-tomosyn-1-gene
#12
Seth R Batten, Elena A Matveeva, Sidney W Whiteheart, Thomas C Vanaman, Greg A Gerhardt, John T Slevin
INTRODUCTION: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling. METHODS: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1(-/-) (Tom(-/-)) animals...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28751143/n-alkyl-1-1-biphenyl-2-sulfonamide-derivatives-as-novel-broad-spectrum-anti-epileptic-drugs-with-efficacy-equivalent-to-that-of-sodium-valproate
#13
Tomoyuki Tanaka, Nana Yajima, Tomoko Kiyoshi, Yoshiki Miura, Seiji Iwama
In order to develop phenyl sulfonamides as a novel class of anti-epileptic drugs (AED) for both general and partial seizure, we initiated in vivo screening of our chemical library in the mice MES and sc-PTZ models and found compounds 1 and 2 as lead compounds. Optimization of 1 and 2 led to the discovery of compound 21, which showed potent anticonvulsant effect in MES, scPTZ and rat amygdala kindling models. These findings indicate that compound 21 could be a useful new broad spectrum AED like sodium valproate and provide an opportunity to struggle current therapy-resistant epilepsy...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
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
#14
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)...
August 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28710841/accelerated-kindling-epileptogenesis-in-tg4510-tau-transgenic-mice-but-not-in-tau-knockout-mice
#15
Shijie Liu, Yu Shen, Sandy R Shultz, Anne Nguyen, Christopher Hovens, Paul A Adlard, Ashley I Bush, Jianxiong Chan, Patrick Kwan, Terence J O'Brien, Nigel C Jones
The biologic processes underlying epileptogenesis following a brain insult are not fully understood, but several lines of evidence suggest that hyperphosphorylation of tau may be an important factor in these processes. To provide further insight into the causal relationship between tau and epileptogenesis, this study applied amygdala kindling to rTg4510 mice that, concurrent with other pathologies, overexpress phosphorylated tau, tau knockout mice, or their respective wild-type controls. Mice were electrically stimulated twice daily, 5 days per week for 3 weeks...
September 2017: Epilepsia
https://www.readbyqxmd.com/read/28674781/spike-densities-of-the-amygdala-and-neocortex-reflect-progression-of-kindled-motor-seizures
#16
Yu-Lin Wang, Sheng-Fu Liang, Alvin W Y Su, Fu-Zen Shaw
Amygdala kindling is a common temporal lobe-like seizure model. In the present study, temporal and spectral analyses of the ictal period were investigated throughout amygdala kindling in response to different behavioral seizures. Right-side amygdala was kindled to induce epileptiform afterdischarges (ADs). ADs of both the frontal cortex and amygdala were analyzed. Powers of the low (0-9 Hz)- and high (12-30 Hz)-frequency bands in response to different behavioral seizures were calculated. Densities of upward and downward peaks of spikes, which reflected information of spike count and spike pattern, throughout kindle-induced ADs were calculated...
January 2018: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/28570965/neurochemical-evidence-based-suggested-therapy-for-safe-management-of-epileptogenesis
#17
Navjot Kaur, Tanveer Singh, Sandeep Kumar, Rajesh Kumar Goel
Most of the clinically available antiepileptic drugs have only antiseizure effects and are reported unable to prevent epileptogenesis. In the past decade, several drugs underwent clinical trials for management of epileptogenesis, but none of the drugs tested was found effective. One of the major lacunas is availability of appropriate preclinical approaches to delineate mechanisms of epileptogenesis. Thus, the present study attempts to suggest a neurochemistry based approach for safe management of epileptogenesis...
July 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28502217/hippocampal-low-frequency-stimulation-inhibits-afterdischarge-and-increases-gaba-a-receptor-expression-in-amygdala-kindled-pharmacoresistant-epileptic-rats
#18
Guofeng Wu, Likun Wang, Zhen Hong, Siying Ren, Feng Zhou
OBJECTIVE: The purpose of the present study was to observe the effects of hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. METHODS: A total of 110 healthy adult male Wistar rats were used to generate a model of epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected from 70 amygdala-kindled rats by testing their response to Phenytoin and Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8 rats)...
August 2017: Neurological Research
https://www.readbyqxmd.com/read/28485718/transcriptional-profile-of-hippocampal-dentate-granule-cells-in-four-rat-epilepsy-models
#19
Raymond Dingledine, Douglas A Coulter, Brita Fritsch, Jan A Gorter, Nadia Lelutiu, James McNamara, J Victor Nadler, Asla Pitkänen, Michael A Rogawski, Pate Skene, Robert S Sloviter, Yu Wang, Wytse J Wadman, Claude Wasterlain, Avtar Roopra
Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression changes. We attempted to minimize these confounds by pooling dentate granule cell transcriptional profiles from 164 rats in seven laboratories, using three status epilepticus (SE) epilepsy models (pilocarpine, kainate, self-sustained SE), plus amygdala kindling...
May 9, 2017: Scientific Data
https://www.readbyqxmd.com/read/28393712/therapeutic-role-of-synaptic-vesicle-glycoprotein-2a-sv2a-in-modulating-epileptogenesis
#20
REVIEW
Yukihiro Ohno, Kentaro Tokudome
Dysfunction of synaptic neurotransmitter release is closely involved in the pathogenesis of various central nervous system diseases. Synaptic vesicle glycoprotein 2A (SV2A) is a membrane protein specifically expressed in synaptic vesicles and it modulates action potential-dependent neurotransmitter release in the brain. Since 1) SV2A-knockout mice exhibit severe convulsive seizures, 2) SV2A expression in the brain is reportedly altered in various epileptic disorders both in animal models (e.g., kindling and genetic models) and humans (e...
2017: CNS & Neurological Disorders Drug Targets
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