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Amygdala kindling

Mostafa Jalilifar, Ali Yadollahpour, Ahmad Ali Moazedi, Zohreh Ghotbeddin
PURPOSE: Determining different seizure stage specific features in a kindling model is a crucial step in developing efficient objective techniques for early prediction and treatment of seizures. This study identified and categorized kindling stages based on their electrophysiological features through processing extracellular field potentials of Amygdala rapid kindling. METHODS: Thirteen Wistar rats (200±10g) were divided into 2 groups including kindle (n=7) and sham (n=6) and respectively underwent an amygdala rapid kindling and placebo stimulation...
September 19, 2016: Brain Research Bulletin
Lubos Remen, Olivier Bezençon, Lloyd Simons, Rick Gaston, Dennis Downing, John Gatfield, Catherine Roch, Melanie Kessler, Johannes Mosbacher, Thomas Pfeifer, Corinna Grisostomi, Markus Rey, Eric A Ertel, Richard Moon
A series of dihydropyrazole derivatives was developed as potent, selective, and brain-penetrating T-type calcium channel blockers. An optimized derivative, compound 6c, was advanced to in vivo studies, where it demonstrated efficacy in the WAG/Rij rat model of generalized nonconvulsive, absence-like epilepsy. Compound 6c was not efficacious in the basolateral amygdala kindling rat model of temporal lobe epilepsy, and it led to prolongation of the PR interval in ECG recordings in rodents.
September 22, 2016: Journal of Medicinal Chemistry
Evy Cleeren, Elsie Premereur, Cindy Casteels, Karolien Goffin, Peter Janssen, Wim Van Paesschen
Epileptic seizures are network-level phenomena. Hence, epilepsy may be regarded as a circuit-level disorder that cannot be understood outside this context. Better insight into the effective connectivity of the seizure onset zone and the manner in which seizure activity spreads could lead to specifically-tailored therapies for epilepsy. We applied the electrical amygdala kindling model in two rhesus monkeys until these animals displayed consistent stage IV seizures. At this stage, we investigated the effective connectivity of the amygdala by means of electrical microstimulation during fMRI (EM-fMRI)...
2016: NeuroImage: Clinical
Kentaro Tokudome, Takahiro Okumura, Ryo Terada, Saki Shimizu, Naofumi Kunisawa, Tomoji Mashimo, Tadao Serikawa, Masashi Sasa, Yukihiro Ohno
Synaptic vesicle glycoprotein 2A (SV2A) is specifically expressed in the membranes of synaptic vesicles and modulates action potential-dependent neurotransmitter release. To explore the role of SV2A in the pathogenesis of epileptic disorders, we recently generated a novel rat model (Sv2a(L174Q) rat) carrying a missense mutation of the Sv2a gene and showed that the Sv2a(L174Q) rats were hypersensitive to kindling development (Tokudome et al., 2016). Here, we further conducted behavioral and neurochemical studies to clarify the pathophysiological mechanisms underlying the seizure vulnerability in Sv2a(L174Q) rats...
2016: Frontiers in Pharmacology
Ruben G F Hendriksen, Sandra Schipper, Govert Hoogland, Olaf E M G Schijns, Jim T A Dings, Marlien W Aalbers, Johan S H Vles
OBJECTIVE: Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. In addition to its role in muscle tissue, it functions as an anchoring protein within the central nervous system such as in hippocampus and cerebellum. Its presence in the latter regions is illustrated by the cognitive problems seen in Duchenne Muscular Dystrophy (DMD). Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability...
2016: Frontiers in Cellular Neuroscience
Shang-Der Chen, Yu-Lin Wang, Sheng-Fu Liang, Fu-Zen Shaw
Amygdala kindling is a model of temporal lobe epilepsy (TLE) with convulsion. The rapid amygdala kindling has an advantage on quick development of motor seizures and for antiepileptic drugs screening. The rapid amygdala kindling causes epileptogenesis accompanied by an anxiolytic response in early isolation of rat pups or depressive behavior in immature rats. However, the effect of rapid amygdala kindling on comorbidity of anxiety- and depression-like behaviors is unexplored in adult rats with normal breeding...
2016: Frontiers in Behavioral Neuroscience
Nihan Çarçak, Ergin Dileköz, Rezzan Gülhan, Rüştü Onur, Filiz Yılmaz Onat, Yıldırım Sara
PURPOSE: Genetic absence epilepsy rats from Strasbourg (GAERS), a well-validated genetic rat model for typical absence epilepsy, are known to manifest a resistance to secondary generalization of abnormal focal electrical activity evoked by kindling. The mechanism of this resistance is still unclear. In order to understand the possible mechanism of kindling resistance, we investigated for the first time, the differences of short-term synaptic plasticity by using a paired-pulse paradigm as an indicator of GABAergic activity in CA1 region of hippocampus in GAERS and non-epileptic Wistar rats in-vivo...
October 2016: Epilepsy Research
Evan Wicker, Patrick A Forcelli
Temporal lobe epilepsy is the most common form of medically-intractable epilepsy. While seizures in TLE originate in structures such as hippocampus, amygdala, and temporal cortex, they propagate through a crucial relay: the midline/intralaminar thalamus. Prior studies have shown that pharmacological inhibition of midline thalamus attenuates limbic seizures. Here, we examined a recently developed technology, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), as a means of chemogenetic silencing to attenuate limbic seizures...
September 2016: Experimental Neurology
J J Botterill, N Nogovitsyn, H J Caruncho, L E Kalynchuk
The vulnerability and plasticity of hippocampal GABAergic interneurons is a topic of broad interest and debate in the field of epilepsy. In this experiment, we used the electrical kindling model of epilepsy to determine whether seizures that originate in different brain regions have differential effects on hippocampal interneuron subpopulations. Long-Evans rats received 99 electrical stimulations of the hippocampus, amygdala, or caudate nucleus, followed by sacrifice and immunohistochemical or western blot analyses...
June 30, 2016: Journal of Comparative Neurology
Shi-Jie Liu, Ping Zheng, David K Wright, Gabi Dezsi, Emma Braine, Thanh Nguyen, Niall M Corcoran, Leigh A Johnston, Christopher M Hovens, Jamie N Mayo, Matthew Hudson, Sandy R Shultz, Nigel C Jones, Terence J O'Brien
There are no treatments in clinical practice known to mitigate the neurobiological processes that convert a healthy brain into an epileptic one, a phenomenon known as epileptogenesis. Downregulation of protein phosphatase 2A, a protein that causes the hyperphosphorylation of tau, is implicated in neurodegenerative diseases commonly associated with epilepsy, such as Alzheimer's disease and traumatic brain injury. Here we used the protein phosphatase 2A activator sodium selenate to investigate the role of protein phosphatase 2A in three different rat models of epileptogenesis: amygdala kindling, post-kainic acid status epilepticus, and post-traumatic epilepsy...
July 2016: Brain: a Journal of Neurology
Kentaro Tokudome, Takahiro Okumura, Saki Shimizu, Tomoji Mashimo, Akiko Takizawa, Tadao Serikawa, Ryo Terada, Shizuka Ishihara, Naofumi Kunisawa, Masashi Sasa, Yukihiro Ohno
Synaptic vesicle glycoprotein 2A (SV2A) is a prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release. SV2A also serves as a specific binding site for certain antiepileptics and is implicated in the treatment of epilepsy. Here, to elucidate the role of SV2A in modulating epileptogenesis, we generated a novel rat model (Sv2a(L174Q) rat) carrying a Sv2a-targeted missense mutation (L174Q) and analyzed its susceptibilities to kindling development. Although animals homozygous for the Sv2a(L174Q) mutation exhibited normal appearance and development, they are susceptible to pentylenetetrazole (PTZ) seizures...
2016: Scientific Reports
Azam Asgari, Saeed Semnanian, Nafiseh Atapour, Amir Shojaei, Homeira Moradi-Chameh, Samireh Ghafouri, Vahid Sheibani, Javad Mirnajafi-Zadeh
Low frequency stimulation (LFS) has been proposed as a new approach in the treatment of epilepsy. The anticonvulsant mechanism of LFS may be through its effect on GABAA receptors, which are the main target of phenobarbital anticonvulsant action. We supposed that co-application of LFS and phenobarbital may increase the efficacy of phenobarbital. Therefore, the interaction of LFS and phenobarbital on GABAergic inhibitory post-synaptic currents (IPSCs) in kindled and control rats was investigated. Animals were kindled by electrical stimulation of basolateral amygdala in a semi rapid manner (12 stimulations/day)...
August 25, 2016: Neuroscience
Jia-Jia Li, Yong-Hua Li, Hai-Qing Gong, Pei-Ji Liang, Pu-Ming Zhang, Qin-Chi Lu
The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amygdala-kindling models during the development of epileptic seizures...
2016: PloS One
Vinícius Rosa Cota, Bruna Marcela Bacellar Drabowski, Jasiara Carla de Oliveira, Márcio Flávio Dutra Moraes
Many patients with epilepsy do not obtain proper control of their seizures through conventional treatment. We review aspects of the pathophysiology underlying epileptic phenomena, with a special interest in the role of the amygdala, stressing the importance of hypersynchronism in both ictogenesis and epileptogenesis. We then review experimental studies on electrical stimulation of mesiotemporal epileptogenic areas, the amygdala included, as a means to treat medically refractory epilepsy. Regular high-frequency stimulation (HFS) commonly has anticonvulsant effects and sparse antiepileptogenic properties...
June 2016: Journal of Neuroscience Research
Carmen Rubio-Osornio, Aldo Eguiluz-Meléndez, Cristina Trejo-Solís, Veronica Custodio, Moises Rubio-Osornio, Artemio Rosiles-Abonce, Juan C Martínez-Lazcano, Edith González, Carlos Paz
The single feature of all malformations in cortical development is the clinical association with epilepsy. It has been proven that Sox-1 expression is essential during neurodevelopment and it is reported that Sox-1 knockout mice present spontaneous generalized seizures. Particularly in cerebellum, Sox-1 plays a key role in the Bergmann´s glia (BG) function, which allows the correct function of the Purkinje cells (PC). The targets of PC are the dentate and interpositus nuclei, which form the main cerebellar efferents involved in the physiopathology of epilepsy...
2016: CNS & Neurological Disorders Drug Targets
Vera Russmann, Josephine D Salvamoser, Maruja L Rettenbeck, Takafumi Komori, Heidrun Potschka
OBJECTIVE: Anticonvulsive monotherapy fails to be effective in one third of patients with epilepsy resulting in the need for polytherapy regimens. However, with the still limited knowledge, drug choices for polytherapy remain empirical. Here we report experimental data from a chronic epilepsy model for the combination of perampanel and zonisamide, which can render guidance for clinical studies and individual drug choices. METHODS: The anticonvulsant effects of the combination of perampanel and zonisamide were evaluated in a rat amygdala kindling model...
April 2016: Epilepsia
Inna Ruiz-Salinas, Luisa Rocha, Bruno A Marichal-Cancino, Carlos M Villalón
Epileptic seizures are often accompanied by increased sympathetic cardiovascular activity (even interictally), but it remains unknown whether this increased activity is of central and/or peripheral origin. Hence, this study investigated the cardiovascular alterations produced by amygdala kindling in awake and pithed Wistar rats. Blood pressure (BP) and heart rate (HR) were initially recorded by tail cuff plethysmography in awake control, sham-operated and amygdala-kindled rats before and 24 hr after the kindling process...
August 2016: Basic & Clinical Pharmacology & Toxicology
Meng Yang, Ezgi Ozturk, Michael R Salzberg, Sandra Rees, Margaret Morris, Terence J O'Brien, Nigel C Jones
OBJECTIVE: Environmental exposures impart powerful effects on vulnerability to many brain diseases, including epilepsy. Mesial temporal lobe epilepsy (MTLE) is a common form of epilepsy, and it is often accompanied by neuropsychiatric comorbidities. This study tests the hypothesis that environmental enrichment (EE) confers antiepileptogenic, psychoprotective, and neuroprotective effects in the amygdala kindling model of MTLE, and explores potential neurobiologic mechanisms. METHODS: At weaning, male Wistar rats were allocated into either EE (large cages containing running wheels and toys; n = 43) or standard housing (SH; standard laboratory cages; n = 39) conditions...
March 2016: Epilepsia
Yu-Lin Wang, Yin-Lin Chen, Alvin Wen-Yu Su, Fu-Zen Shaw, Sheng-Fu Liang
Epileptogenesis, which occurs in an epileptic brain, is an important focus for epilepsy. The spectral analysis has been popularly applied to study the electrophysiological activities. However, the resolution is dominated by the window function of the algorithm used and the sample size. In this report, a temporal waveform analysis method is proposed to investigate the relationship of electrophysiological discharges and motor outcomes with a kindling process. Wistar rats were subjected to electrical amygdala kindling to induce temporal lobe epilepsy...
March 2016: IEEE Transactions on Neural Systems and Rehabilitation Engineering
Yang Liu, Yi Wang, Zheng-hao Xu, Zhong Chen
OBJECTIVE: To investigate the antiepileptic effects of various stimulation modes of low-frequency stimulation(LFS) on the kindling rats. METHODS: Stimulating electrodes were implanted in the amygdala and current with constant intensity was applied to evoke kindling-induced seizures. The antiepileptic effect of LFS by open loop stimulation(before kindling), closed loop stimulation(immediately after kindling) and different forms of closed loop stimulation(whole stage after kindling and early stage after kindling) were investigated in amygdala kindled rats...
September 2015: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
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