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https://www.readbyqxmd.com/read/29148909/inhibition-of-gaba-transporters-fails-to-afford-significant-protection-following-focal-cerebral-ischemia
#1
Maria Ek Lie, Emma K Gowing, Rasmus P Clausen, Petrine Wellendorph, Andrew N Clarkson
Brain ischemia triggers excitotoxicity and cell death, yet no neuroprotective drugs have made it to the clinic. While enhancing GABAergic signaling to counterbalance excitotoxicity has shown promise in animal models, clinical studies have failed. Blockade of GABA transporters (GATs) offers an indirect approach to increase GABA inhibition to lower the excitation threshold of neurons. Among the GATs, GAT1 is known to promote neuroprotection, while the protective role of the extrasynaptic transporters GAT3 and BGT1 is elusive...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29137682/cefepime-induced-neurotoxicity-a-systematic-review
#2
Lauren E Payne, David J Gagnon, Richard R Riker, David B Seder, Elizabeth K Glisic, Jane G Morris, Gilles L Fraser
BACKGROUND: Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations...
November 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29128586/contraception-pregnancy-and-peripartum-experiences-among-women-with-epilepsy-in-bhutan
#3
Sheliza Halani, Lhab Tshering, Esther Bui, Sarah J Clark, Sara J Grundy, Tandin Pem, Sonam Lhamo, Ugyen Dema, Damber K Nirola, Chencho Dorji, Farrah J Mateen
INTRODUCTION: Reports on the reproductive health of women with epilepsy (WWE) in low- and middle-income countries (LMICs) are limited. Bhutan is a lower income country with a high estimated prevalence of epilepsy and no out-of-pocket payment requirements for health visits or medications. METHODS: We developed a 10-category survey to interview WWE ages 20-59 years in the Kingdom of Bhutan to understand their contraceptive use and peripartum experiences. WWE were recruited from 2016-2017 from an existing epilepsy cohort and their reproductive health data were merged with epilepsy and socioeconomic data obtained from initial clinical evaluations performed between 2014 and 2016...
October 18, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29128469/the-different-patterns-of-seizure-induced-aphasia-in-temporal-lobe-epilepsies
#4
Agnès Trebuchon, Isabelle Lambert, Bernard Guisiano, Aileen McGonigal, Charline Perot, Francesca Bonini, Romain Carron, Catherine Liegeois-Chauvel, Patrick Chauvel, Fabrice Bartolomei
OBJECTIVES: Ictal language disturbances may occur in dominant hemisphere temporal lobe epilepsy (TLE), but little is known about the precise anatomoelectroclinical correlations. This study investigated the different facets of ictal aphasia in intracerebrally recorded TLE. METHODS: Video-stereoelectroencephalography (SEEG) recordings of 37 seizures in 17 right-handed patients with drug-resistant TLE were analyzed; SEEG electroclinical correlations between language disturbance and involvement of temporal lobe structures were assessed...
November 8, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29127761/seizure-vulnerability-and-anxiety-responses-following-chronic-co-administration-and-acute-withdrawal-of-caffeine-and-ethanol-in-a-rat-model
#5
Daniel Matovu, Paul E Alele
BACKGROUND: Caffeine antagonizes the intoxicating effects of alcohol. Consequently, there has been a dramatic global increase in the consumption of caffeinated drinks together with alcohol, especially among young adults. We assessed the seizure vulnerability and anxiety responses following the chronic co-administration of, and withdrawal from, caffeine and ethanol in male rats. METHODS: The rats were randomly assigned to six groups consisting of 10 animals each: 10 mg/kg of caffeine, 20 mg/kg of caffeine, 4 g/kg of 20% ethanol, combined caffeine (20 mg/kg) and ethanol (4 g/kg of 20%), 4 mL/kg distilled water, and an untreated control group...
November 11, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29104044/calcitonin-potentiates-the-anticonvulsant-and-antinociceptive-effects-of-valproic-acid-and-pregabalin-in-pentylenetetrazole-kindled-mice
#6
Nada M Hamada, Rehab H Ashour, Amany A Shalaby, Hussien M El-Beltagi
Antiepileptic drugs are the backbone for epilepsy management. Epilepsy may be accompanied by decreased pain threshold. Thus, anticonvulsant agents with antinociceptive properties are of great importance. This study investigated the possible anticonvulsant and antinociceptive effects of calcitonin in combination with either valproic acid or pregabalin and whether these effects might occur through γ-aminobutyric acid (GABA) modulation. Eighty-four male Balb/C mice were divided into 7 groups: control-naïve, pentylenetetrazole (PTZ)-induced seizures, PTZ-calcitonin, PTZ-valproic acid, PTZ-pregabalin, PTZ-calcitonin-valproic acid (PCV) combination, and PTZ-calcitonin-pregabalin (PCP) combination...
November 2, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29095003/-spanish-multicenter-study-hyperammonemia-not-associated-with-inborn-errors-of-metabolism-in-children
#7
Mercedes Gil Campos, Javier Blasco-Alonso, Concepción Sierra Córcoles, José Luis Cuevas Cervera, Luisa Arrabal Fernández, Luis Aldámiz Echevarría, Amaya Belanger
INTRODUCTION: The hyperammonemic encephalopathy induced by causes different from inborn errors of metabolism is a relatively uncommon but severe complication. OBJETIVES: To study the characteristics of a secondary hyperammonemia episode to discern the triggering causes to get to the diagnosis, and the development in the therapeutic intervention. METHODS: A multicenter retrospective study of children with hyperammonemia unrelated to inborn errors of metabolism, conducted in Spanish hospitals...
July 28, 2017: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/29080083/evaluation-of-metformin-effects-in-the-chronic-phase-of-spontaneous-seizures-in-pilocarpine-model-of-temporal-lobe-epilepsy
#8
Soraya Mehrabi, Nima Sanadgol, Mahmood Barati, Ali Shahbazi, Gelareh Vahabzadeh, Mitra Barzroudi, Morteza Seifi, Mazaher Gholipourmalekabadi, Fereshteh Golab
Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB)...
October 27, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29074125/status-epilepticus-triggers-long-lasting-activation-of-complement-c1q-c3-signaling-in-the-hippocampus-that-correlates-with-seizure-frequency-in-experimental-epilepsy
#9
Nicole D Schartz, Season K Wyatt-Johnson, Lauren R Price, Samantha A Colin, Amy L Brewster
Status epilepticus (SE) triggers a myriad of neurological alterations that include unprovoked seizures, temporal lobe epilepsy (TLE), and cognitive deficits. Although SE-induced loss of hippocampal dendritic structures and synaptic remodeling are often associated with this pathophysiology, the underlying mechanisms remain elusive. Recent evidence points to the classical complement pathway as a potential mechanism. Signaling through the complement protein C1q to C3, which is cleaved into smaller biologically active fragments including C3b and iC3b, contributes to the elimination of synaptic structures in the normal developing brain and in models of neurodegenerative disorders...
October 23, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29071470/the-challenge-of-pharmacotherapy-in-children-and-adolescents-with-epilepsy-adhd-comorbidity
#10
REVIEW
Alberto Verrotti, Romina Moavero, Gianvito Panzarino, Claudia Di Paolantonio, Renata Rizzo, Paolo Curatolo
Epilepsy is common in children and adolescents where its prevalence is 3.2-5.5/1000. About one-third of patients also have attention deficit hyperactivity/impulsivity disorder (ADHD). The possible relationship between epilepsy and ADHD is still unclear, and ADHD symptoms (such as inattention, hyperactivity, behavioral disturbances) are frequently considered as adverse effects of antiepileptic drugs (AEDs). The literature was searched for data on the behavioral effects of AEDs. Phenobarbital is the most frequently reported medication to induce symptoms of ADHD, followed by topiramate and valproic acid...
October 25, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29070499/identifying-and-characterizing-preventable-adverse-drug-events-for-prioritizing-pharmacist-intervention-in-hospitals
#11
Nakyung Jeon, Ben Staley, Thomas Johns, Glori Pflugfelder Lipori, Babette Brumback, Richard Segal, Almut G Winterstein
PURPOSE: The approach and results for identifying and characterizing preventable adverse drug events (pADEs) that are key targets for pharmacist medication therapy management (MTM) are summarized. METHODS: This study was part of a larger effort aimed at developing an electronic health record-based prediction model (the complexity score, or C-score) that ranks hospitalized patients according to their risk for pADEs. An environmental scan of published epidemiologic pADE studies and national patient safety priority areas was conducted...
November 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29061647/pyridoxine-dependent-epilepsy-in-zebrafish-caused-by-aldh7a1-deficiency
#12
Izabella A Pena, Yann Roussel, Kate Daniel, Kevin Mongeon, Devon Johnstone, Hellen Weinschutz Mendes, Marjolein Bosma, Vishal Saxena, Nathalie Lepage, Pranesh Chakraborty, David A Dyment, Clara D M van Karnebeek, Nanda Verhoeven-Duif, Tuan Vu Bui, Kym M Boycott, Marc Ekker, Alex MacKenzie
Pyridoxine-dependent epilepsy (PDE) is a rare disease characterized by mutations in the lysine degradation gene ALDH7A1 leading to recurrent neonatal seizures which are uniquely alleviated by high doses of pyridoxine or pyridoxal 5'-phosphate (vitamin B6 vitamers). Despite treatment, neurodevelopmental disabilities are still observed in most PDE patients underlining the need for adjunct therapies. Over 60 years after the initial description of PDE, we report the first animal model for this disease: an aldh7a1-null zebrafish (Danio rerio) displaying deficient lysine metabolism and spontaneous and recurrent seizures in the larval stage (10 dpf)...
October 23, 2017: Genetics
https://www.readbyqxmd.com/read/29056747/prrt2-deficiency-induces-paroxysmal-kinesigenic-dyskinesia-by-regulating-synaptic-transmission-in-cerebellum
#13
Guo-He Tan, Yuan-Yuan Liu, Lu Wang, Kui Li, Ze-Qiang Zhang, Hong-Fu Li, Zhong-Fei Yang, Yang Li, Dan Li, Ming-Yue Wu, Chun-Lei Yu, Juan-Juan Long, Ren-Chao Chen, Li-Xi Li, Lu-Ping Yin, Ji-Wei Liu, Xue-Wen Cheng, Qi Shen, You-Sheng Shu, Kenji Sakimura, Lu-Jian Liao, Zhi-Ying Wu, Zhi-Qi Xiong
Mutations in the proline-rich transmembrane protein 2 (PRRT2) are associated with paroxysmal kinesigenic dyskinesia (PKD) and several other paroxysmal neurological diseases, but the PRRT2 function and pathogenic mechanisms remain largely obscure. Here we show that PRRT2 is a presynaptic protein that interacts with components of the SNARE complex and downregulates its formation. Loss-of-function mutant mice showed PKD-like phenotypes triggered by generalized seizures, hyperthermia, or optogenetic stimulation of the cerebellum...
October 20, 2017: Cell Research
https://www.readbyqxmd.com/read/29053577/electrographic-changes-accompanying-recurrent-seizures-under-ketogenic-diet-treatment
#14
Chiara Lucchi, Maddalena Marchiò, Elisa Caramaschi, Carmela Giordano, Rocco Giordano, Azzurra Guerra, Giuseppe Biagini
The ketogenic diet (KD) is increasingly used to treat epilepsy refractory to antiepileptic drugs and other neurological disorders. In animal models, the KD was found to increase the threshold to seizures induced by different convulsive stimulations. However, in models in which suprathreshold stimuli were used, a paradoxical seizure worsening was consistently observed in KD-fed animals. To better define this phenomenon, we characterized the electrographic response to seizures induced in mice which were treated with the KD, and then corneally stimulated at 6-Hz in four different sessions...
October 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29042752/spotlight-on-perampanel-in-the-management-of-seizures-design-development-and-an-update-on-place-in-therapy
#15
REVIEW
Michele A Faulkner
PURPOSE: Perampanel is a first-in-class antiepileptic medication approved for the treatment of partial (focal) seizures, and as adjunctive treatment for primarily generalized tonic-clonic seizures. The pharmacology, efficacy data, adverse-effect profile, pharmacokinetics and place in therapy are reviewed. SUMMARY: Perampanel is indicated for use in patients with epilepsy who are 12 years of age or older. It is the first medication designed specifically to be a non-competitive antagonist at post-synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29034101/lamotrigine-induced-sexual-dysfunction-and-non-adherence-case-analysis-with-literature-review
#16
Kenneth R Kaufman, Melissa Coluccio, Kartik Sivaraaman, Miriam Campeas
BACKGROUND: Optimal anti-epileptic drug (AED) treatment maximises therapeutic response and minimises adverse effects (AEs). Key to therapeutic AED treatment is adherence. Non-adherence is often related to severity of AEs. Frequently, patients do not spontaneously report, and clinicians do not specifically query, critical AEs that lead to non-adherence, including sexual dysfunction. Sexual dysfunction prevalence in patients with epilepsy ranges from 40 to 70%, often related to AEDs, epilepsy or mood states...
September 2017: BJPsych Open
https://www.readbyqxmd.com/read/29033486/topiramate-induced-acute-liver-injury-a-rare-adverse-effect
#17
Archish Khivsara, Jeffrey Pradeep Raj, Divya Hegde, Mangala Rao
Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or predictable DILI. Although it is common in first-generation antiepileptic drugs (AEDs), it is rare in newer AEDs such as topiramate. Topiramate commonly causes neurological adverse effects such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare and has been previously reported in combination with other drugs such as valproate and carbamazepine. Here, we report a case of topiramate-induced asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol dependence syndrome and alcohol withdrawal complicated with seizures...
May 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29032429/dna-damage-and-oxidative-stress-induced-by-seizures-are-decreased-by-anticonvulsant-and-neuroprotective-effects-of-lobeline-a-candidate-to-treat-alcoholism
#18
Liana Dantas da Costa E Silva, Patrícia Pereira, Gabriela Gregory Regner, Fernanda Brião Menezes Boaretto, Cleonice Hoffmann, Pricila Pflüger, Lucas Lima da Silva, Luiza Reinhardt Steffens, Ana Moira Morás, Dinara Jaqueline Moura, Jaqueline Nascimento Picada
The alkaloid lobeline (Lob) has been studied due to its potential use in treatment of drug abuse. This study evaluates the possible anticonvulsant and neuroprotective activities of Lob to obtain new information on its properties that could confirm it as a candidate in the treatment of alcohol addiction. The anticonvulsant effect of Lob was evaluated using a pilocarpine-induced seizure model. In addition, possible neuroprotective effects were investigated measuring DNA damage using the comet assay, assessing free radical levels by dichlorofluorescein diacetate (DCF) oxidation, and measuring the antioxidant potential using the α, α-diphenyl-β-picrylhydrazyl (DPPH) scavenging assay, besides measuring superoxide dismutase (SOD) and catalase (CAT) enzyme activities in brain tissues...
October 14, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29032011/sitagliptin-enhances-the-neuroprotective-effect-of-pregabalin-against-pentylenetetrazole-induced-acute-epileptogenesis-in-mice-implication-of-oxidative-inflammatory-apoptotic-and-autophagy-pathways
#19
Manar A Nader, Hayam Ateyya, Mohamed El-Shafey, Nagla A El-Sherbeeny
The current investigation aimed at studying the anti-epileptogenic effect of sitagliptin. The possible effect of the drug in combination with pregabalin in pentylenetetrazole (PTZ)- induced seizures was studied. In addition, the postulated mechanisms that could mediate such effect were explored namely, suppression of oxidative stress and neuro-inflammatory markers, autophagy and apoptosis. Seven days prior to PTZ (60 mg/kg, sc) injection, mice were treated with sitagliptin (5, 15, and 60 mg/kg, twice daily, orally) or pregabalin (30 mg/kg, once daily, orally) or their combination...
October 11, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#20
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
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