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https://www.readbyqxmd.com/read/29783181/autistic-traits-in-epilepsy-models-why-when-and-how
#1
REVIEW
Jana Velíšková, Jill L Silverman, Melissa Benson, Pierre-Pascal Lenck-Santini
Autism spectrum disorder (ASD) is a common comorbidity of epilepsy and seizures and/or epileptiform activity are observed in a significant proportion of ASD patients. Current research also implies that autistic traits can be observed to a various degree in mice and rats with seizures. This suggests that there are shared mechanisms in both ASD and epilepsy syndromes. Here, we first review the standard, validated methods used to assess autistic traits in animal models as well as their limitations with regards to epilepsy models...
May 18, 2018: Epilepsy 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
#2
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/29778462/altered-mitochondrial-acetylation-profiles-in-a-kainic-acid-model-of-temporal-lobe-epilepsy
#3
Lindsey B Gano, Li-Ping Liang, Kristen Ryan, Cole R Michel, Joe Gomez, Athanassios Vassilopoulos, Nichole Reisdorph, Kristofer S Fritz, Manisha Patel
Impaired bioenergetics and oxidative damage in the mitochondria are implicated in the etiology of temporal lobe epilepsy, and hyperacetylation of mitochondrial proteins has recently emerged as a critical negative regulator of mitochondrial functions. However, the roles of mitochondrial acetylation and activity of the primary mitochondrial deacetylase, SIRT3, have not been explored in acquired epilepsy. We investigated changes in mitochondrial acetylation and SIRT3 activity in the development of chronic epilepsy in the kainic acid rat model of TLE...
May 17, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29777902/chemical-characterization-and-cerebroprotective-effect-of-methanolic-root-extract-of-colebrookea-oppositifolia-in-rats
#4
Gollapalle Lakshminarayanashastry Viswanatha, Marikunte V Venkataranganna, Nunna Bheema Lingeswara Prasad, Shylaja Hanumanthappa
ETHNOPHARMACOLOGICAL RELEVANCE: Colebrookea oppositifolia Smith is one of the extensively used plants to treat neurological conditions such as epilepsy by the various ethnic communities in sub-Himalayan regions of India such as Bhoxa, Tharu and nomadic Gujjars. AIM OF THE STUDY: This study was conducted to evaluate the cerebroprotective effect of C. oppositifolia methanolic root (MeCO) extract in Wistar rats. MATERIALS AND METHODS: The MeCO was characterized for total phenolic content and later subjected for detailed liquid chromatography-mass spectrometry analysis...
May 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29776417/sinomenine-exerts-anticonvulsant-profile-and-neuroprotective-activity-in-pentylenetetrazole-kindled-rats-involvement-of-inhibition-of-nlrp1-inflammasome
#5
Bo Gao, Yu Wu, Yuan-Jian Yang, Wei-Zu Li, Kun Dong, Jun Zhou, Yan-Yan Yin, Da-Ke Huang, Wen-Ning Wu
BACKGROUND: Epilepsy is a common neurological disorder and is not well controlled by available antiepileptic drugs (AEDs). Inflammation is considered to be a critical factor in the pathophysiology of epilepsy. Sinomenine (SN), a bioactive alkaloid with anti-inflammatory effect, exerts neuroprotective activity in many nervous system diseases. However, little is known about the effect of SN on epilepsy. METHODS: The chronic epilepsy model was established by pentylenetetrazole (PTZ) kindling...
May 18, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29774448/the-expression-alteration-of-bc1-rna-and-its-interaction-with-eukaryotic-translation-initiation-factor-eif4a-post-status-epilepticus
#6
Xiangchang Zeng, Wenjing Zong, Qing Gao, Siyu Chen, Lulu Chen, Guirong Zeng, Weihua Huang, Zhenyu Li, Chang Zeng, Yuanyuan Xie, Xiaohui Li, Bo Xiao, Dongsheng-Ouyang, Kai Hu
Abnormal dendritic sprouting and synaptic remodelling are important pathological features of temporal lobe epilepsy. BC1 RNA is a translation repressor involved in the regulation of the dendritic protein synthesis and mRNA transport, which is essential for dendritic development and plasticity. The expression alteration of BC1 RNA in the pilocarpine induced epilepsy model remains unknown. It is unclear if the interactions between BC1 RNA and eukaryotic initiation factor 4A (eIF4A) exists in this model. The purpose of this study was to investigate the expression changes of BC1 RNA and its interactions with eIF4A post-status epilepticus (SE)...
May 17, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29772999/pharmacological-evaluation-of-novel-flavone-from-morus-alba-in-pentylenetetrazole-induced-kindling-and-oxidative-stress
#7
Bin Wang, Gaurav Gupta, Mahaveer Singh, Kasturi Vishwanatha Setty Veerabhadrappa, Anurag Mishra, Gopala Krishna Chinnaboina
The present study was designed to explore the effect of chronic administration of a new flavone [morusflavone, 5,7,4'-trihydroxy-8-(γ,γ-dimethylallyl)-2',3'-(10'-hydroxy-9',10'-dimethyl-cyclohex-8-enyl)-flavone (compound 1)] at doses of 25, 50, and 100 mg/kg, orally (p.o.) to pentylenetetrazole-induced kindling in rats (a model of human epilepsy). Compound 1 and four other compounds were isolated from the stem bark of Morus alba. The structure of compound 1 was elucidated and established using standard spectroscopic techniques, and malondialdehyde (MDA) and glutathione (GSH) were estimated as oxidative markers in brain tissues of rodents...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29772217/altered-activity-and-information-flow-in-the-default-mode-network-of-pilocarpine-induced-epilepsy-rats
#8
Yan Cui, Shuang Yu, Tianjiao Zhang, Yangsong Zhang, Yang Xia, Dezhong Yao, Daqing Guo
Temporal lobe epilepsy (TLE) is considered a brain activity disorder that is likely related to allomnesia and conscious disturbance. In rodents, TLE epileptiform discharges can be triggered by systemic administration of a dose of pilocarpine. However, how these pilocarpine-induced epileptiform discharges generate and propagate through the whole brain has not been well studied. In this study, we sought to assess alterations of activity and information flow in the default mode network (DMN) during TLE epileptiform discharges in pilocarpine-induced TLE rats...
May 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29766039/beneficial-outcome-of-urethane-treatment-following-status-epilepticus-in-a-rat-organophosphorus-toxicity-model
#9
Asheebo Rojas, Wenyi Wang, Avery Glover, Zahra Manji, Yujiao Fu, Raymond Dingledine
The efficacy of benzodiazepines to terminate electrographic status epilepticus (SE) declines the longer a patient is in SE. Therefore, alternative methods for ensuring complete block of SE and refractory SE are necessary. We compared the ability of diazepam and a subanesthetic dose of urethane to terminate prolonged SE and mitigate subsequent pathologies. Adult Sprague Dawley rats were injected with diisopropylfluorophosphate (DFP) to induce SE. Rats were administered diazepam (10 mg/kg, ip) or urethane (0...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29766029/seizure-suppressant-and-neuroprotective-effects-of-encapsulated-bdnf-producing-cells-in-a-rat-model-of-temporal-lobe-epilepsy
#10
Chiara Falcicchia, Giovanna Paolone, Dwaine F Emerich, Francesca Lovisari, William J Bell, Tracie Fradet, Lars U Wahlberg, Michele Simonato
Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%. These benefits were associated with improved cognitive performance, as epileptic rats treated with BDNF performed significantly better on a novel object recognition test...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29765321/brain-lipopolysaccharide-preconditioning-induced-gene-reprogramming-mediates-a-tolerance-state-in-electroconvulsive-shock-model-of-epilepsy
#11
Elham Amini, Mojtaba Golpich, Abdoreza S Farjam, Behnam Kamalidehghan, Zahurin Mohamed, Norlinah M Ibrahim, Abolhassan Ahmadiani, Azman A Raymond
There is increasing evidence pointing toward the role of inflammatory processes in epileptic seizures, and reciprocally, prolonged seizures induce more inflammation in the brain. In this regard, effective strategies to control epilepsy resulting from neuroinflammation could be targeted. Based on the available data, preconditioning (PC) with low dose lipopolysaccharide (LPS) through the regulation of the TLR4 signaling pathway provides neuroprotection against subsequent challenge with injury in the brain. To test this, we examined the effects of a single and chronic brain LPS PC, which is expected to lead to reduction of inflammation against epileptic seizures induced by electroconvulsive shock (ECS)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29763644/immunomodulatory-effect-of-celecoxib-on-hmgb1-tlr4-pathway-in-a-recurrent-seizures-model-in-immature-rats
#12
Mariana Morales-Sosa, Sandra Orozco-Suárez, AngélicaVega-García, Sara Caballero-Chacón, Iris A Feria-Romero
Epileptic seizures constitute an important problem in pediatric neurology during the developmental period. The frequency and nosological significance of seizures, as well as their association with epileptogenesis, may be related to underlying mechanisms such as neuroinflammation. Those mechanisms of response activate inflammatory molecules induced in the neurons, activated glial cells and endothelial cells via the key HMGB1/TLR4 pathway. In this study, the drug celecoxib (CCX) was used as a blocker of the cyclooxygenase 2 (COX-2) and HMGB1/TLR-4 pathways...
May 12, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29762840/the-effect-of-mir-146a-gene-silencing-on-drug-resistance-and-expression-of-protein-of-p-gp-and-mrp1-in-epilepsy
#13
H-L Zhang, Y-H Lin, Y Qu, Q Chen
OBJECTIVE: To investigate the effect of miR-146a gene silencing on brain tissue and related drug-resistance proteins in rats and explore its resistance mechanism. MATERIALS AND METHODS: A rat model of chronic refractory epilepsy was established. The rats were divided into four groups: Normal group, Model group, Negative control group and AntagomiR-146a group. Hematoxylin and eosin (HE) stain was used to detect brain histopathological changes. We examined the expression of mRNA of miR-146a, multidrug resistance (MDR1) and multidrug-resistant associated protein (MRP1) by RT-PCR...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29758341/effect-of-zembrin-%C3%A2-and-four-of-its-alkaloid-constituents-on-electric-excitability-of-the-rat-hippocampus
#14
Wilfried Dimpfel, Richard Franklin, Nigel Gericke, Leonie Schombert
ETHNOPHARMACOLOGICAL RELEVANCE: Sceletium tortuosum (Mesembryanthemaceae), a succulent plant indigenous to South Africa. is consumed in the form of teas, decoctions and tinctures and is sometimes smoked and used as snuff. In recent years, Sceletium has received a great deal of commercial interest for relieving stress in healthy people, and for treating a broad range of psychological, psychiatric and inflammatory conditions. MATERIAL AND METHODS: The whole extract (Zembrin®) was tested ex vivo in the hippocampus slice preparation after one week of daily oral administration of 5 and 10mg/kg...
May 11, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29755351/gastrodin-attenuates-bilateral-common-carotid-artery-occlusion-induced-cognitive-deficits-via-regulating-a%C3%AE-related-proteins-and-reducing-autophagy-and-apoptosis-in-rats
#15
Bo Liu, Jian-Mei Gao, Fei Li, Qi-Hai Gong, Jing-Shan Shi
Gastrodin (GAS), an active constituent extracted from Gastrodia elata Blume, is used to treat ischemic stroke, epilepsy, dizziness, and dementia for centuries in China. This study examined its effects on vascular dementia (VD) and the underlying molecular mechanisms. VD was established by ligation of bilateral common carotid artery occlusion (BCCAO). A total of 7 days after BCCAO surgery, GAS (15, 30, and 60 mg/kg) was orally administered for 28 consecutive days to evaluate therapeutic effects. Cognitive function was tested by the Morris water maze...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29754109/improving-effect-of-mild-foot-electrical-stimulation-on-pentylenetetrazole-induced-impairment-of-learning-and-memory
#16
Monir Abasi-Moghadam, Arefe Ghasemi-Dehno, Mehdi Sadegh, Mohammad Reza Palizvan
Epilepsy is a common neurological disorder that affects learning and memory. Recently it has been shown that mild foot electrical stimulation (MFES) can increase learning and memory in normal rats. Pentylenetetrazole (PTZ) kindling is a model of human epilepsy. As with human epilepsy, PTZ kindling impairs learning and memory in rats. The purpose of this study was to investigate the effect MFES on kindling-induced learning and memory deficits in rats. Forty-nine male Wistar rats weighting 200 to 250 g were divided into the following seven groups: PTZ only, phenytoin only, MFES only, PTZ plus phenytoin, PTZ plus MFES, phenytoin plus MFES, and saline (control), with the treatments administered for 26 days...
May 10, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29753106/feasibility-of-imaging-evoked-activity-throughout-the-rat-brain-using-electrical-impedance-tomography
#17
Mayo Faulkner, Sana Hannan, Kirill Aristovich, James Avery, David Holder
Electrical Impedance Tomography (EIT) is an emerging technique which has been used to image evoked activity during whisker displacement in the cortex of an anaesthetised rat with a spatiotemporal resolution of 200 μm and 2 ms. The aim of this work was to extend EIT to image not only from the cortex but also from deeper structures active in somatosensory processing, specifically the ventral posterolateral (VPL) nucleus of the thalamus. The direct response in the cortex and VPL following 2 Hz forepaw stimulation were quantified using a 57-channel epicortical electrode array and a 16-channel depth electrode...
May 9, 2018: NeuroImage
https://www.readbyqxmd.com/read/29752287/-rnaset2-knockout-rats-exhibit-hippocampal-neuropathology-and-deficits-in-memory
#18
Kerstin W Sinkevicius, Thomas R Morrison, Praveen Kulkarni, Martha K Caffrey Cagliostro, Sade Iriah, Samantha Malmberg, Julia Sabrick, Jennifer A Honeycutt, Kim L Askew, Malav Trivedi, Craig F Ferris
RNASET2 deficiency in humans is associated with infant cystic leukoencephalopathy, which causes psychomotor impairment, spasticity, and epilepsy. A zebrafish mutant model suggests that loss of RNASET2 function leads to neurodegeneration due to the accumulation of non-degraded RNA in the lysosomes. The goal of this study was to characterize the first rodent model of RNASET2 deficiency. The brains of 3- and 12-month-old RNaseT2 knockout rats were studied using multiple magnetic resonance imaging modalities and behavioral tests...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29751355/targeting-of-microrna-21-5p-protects-against-seizure-damage-in-a-kainic-acid-induced-status-epilepticus-model-via-pten-mtor
#19
Chongyang Tang, Yunhe Gu, Haiyang Wang, Hongmei Wu, Yu Wang, Yao Meng, Zhibin Han, Yifei Gu, Wei Ma, Zhenfeng Jiang, Yuanyuan Song, Meng Na, Dunyue Lu, Zhiguo Lin
OBJECTIVE: Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target messenger (m)RNA. The present study aims to determine the changes associated with microRNA-21-5p (miR-21-5p) during epileptogenesis in a kainic acid rat model, and to assess whether the PTEN-mTOR pathway is a target of miR-21-5p. METHOD: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the quantitative expressions of miR-21-5p and PTEN, and Western blotting was used to test the activity of mTOR in the acute, latent, and chronic stages of epileptogenesis...
May 4, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29751140/nanoparticle-based-delivery-of-carbamazepine-a-promising-approach-for-the-treatment-of-refractory-epilepsy
#20
Anna Zybina, Anastasiya Anshakova, Julia Malinovskaya, Pavel Melnikov, Vladimir Baklaushev, Vladimir Chekhonin, Olga Maksimenko, Sergey Titov, Vadim Balabanyan, Jörg Kreuter, Svetlana Gelperina, Kenul Abbasova
Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy...
May 8, 2018: International Journal of Pharmaceutics
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