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epilepsy pathophysiology

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https://www.readbyqxmd.com/read/28624414/corneal-kindled-c57bl-6-mice-exhibit-saturated-dentate-gyrus-long-term-potentiation-and-associated-memory-deficits-in-the-absence-of-overt-neuron-loss
#1
Gregory J Remigio, Jaycie L Loewen, Sage Heuston, Colin Helgeson, H Steve White, Karen S Wilcox, Peter J West
Memory deficits have a significant impact on the quality of life of patients with epilepsy and currently no effective treatments exist to mitigate this comorbidity. While these cognitive comorbidities can be associated with varying degrees of hippocampal cell death and hippocampal sclerosis, more subtle changes in hippocampal physiology independent of cell loss may underlie memory dysfunction in many epilepsy patients. Accordingly, animal models of epilepsy or epileptic processes exhibiting memory deficits in the absence of cell loss could facilitate novel therapy discovery...
June 14, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28623837/abnormal-asymmetry-in-benign-epilepsy-with-unilateral-and-bilateral-centrotemporal-spikes-a-combined-fmri-and-dti-study
#2
Weifang Cao, Yaodan Zhang, Changyue Hou, Fei Yang, Jinnan Gong, Sisi Jiang, Yue Huang, Ruhui Xiao, Cheng Luo, Xiaoming Wang, Dezhong Yao
Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic focal childhood epilepsy associated with either unilateral or bilateral epileptic discharge. Asymmetry as an important characteristic of the human brain is beneficial for brain functions. However, little is known about on asymmetry of BECTS patients with different epileptic spikes pattern. In the present study, we investigated functional and structural asymmetries in unilateral spikes BECTS (U_BECTS) patients and bilateral spikes BECTS (B_BECTS) patients using resting state functional magnetic resonance images and diffusion tensor imaging...
June 8, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28611548/hippocampal-characteristics-and-invariant-sequence-elements-distribution-of-glra2-and-glra3-c-to-u-editing
#3
Philipp Schaefermeier, Sarah Heinze
Glycine receptor α2 and α3 subunit (GLRA2/GLRA3) high-affinity variants, of which the subjacent amino acid substitutions issue from C-to-U RNA editing, are thought to influence tonic inhibition and pathophysiology. In light of the detection of GLRA3 NM_006529:r.1157C>U and GLRA2 NM_002063:r.1416C>U exchanges in hippocampus explants of temporal lobe epilepsy patients, we now examine the healthy situation and relate it to the epileptic situation by ascertaining controls in a legitimate reanalysis. The GLRA2 and GLRA3 editing events that would ultimately result in a glycine receptor with increased affinity occur in the postmortem nonepileptic hippocampus...
March 2017: Molecular Syndromology
https://www.readbyqxmd.com/read/28608537/inhibition-of-human-n-and-t-type-calcium-channels-by-an-ortho-phenoxyanilide-derivative-moniro-1
#4
Jeffrey R McArthur, Leonid Motin, Ellen C Gleeson, Sandro Spiller, Richard J Lewis, Peter J Duggan, Kellie L Tuck, David J Adams
BACKGROUND AND PURPOSE: Voltage-gated calcium channels are involved in peripheral and central nervous system nociception. N-type (Cav 2.2) and T-type (Cav 3.1, Cav 3.2 and Cav 3.3) voltage-gated calcium channels are particularly important in studying and treating pain and epilepsy. EXPERIMENTAL APPROACH: In this study, whole-cell patch clamp electrophysiology was used to assess the potency and mechanism of action of a novel ortho-phenoxylanilide derivative, MONIRO-1, against a panel of voltage-gated calcium channels including Cav 1...
June 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28591482/hypothalamic-hamartoma-epileptogenesis-beyond-the-lesion
#5
Julia Scholly, Anke Maren Staack, Philippe Kahane, Didier Scavarda, Jean Régis, Edouard Hirsch, Fabrice Bartolomei
The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling-like secondary epileptogenesis has been suggested as a possible underlying mechanism...
June 2017: Epilepsia
https://www.readbyqxmd.com/read/28591479/hypothalamic-hamartoma-with-epilepsy-review-of-endocrine-comorbidity
#6
Victor S Harrison, Oliver Oatman, John F Kerrigan
The most common, and usually the only, endocrine disturbance in patients with hypothalamic hamartoma (HH) and epilepsy is central precocious puberty (CPP). The mechanism for CPP associated with HH may relate to ectopic generation and pulsatile release of gonadotropin-releasing hormone (GnRH) from the HH, but this remains an unproven hypothesis. Possible regulators of GnRH release that are intrinsic to HH tissue include the following: (1) glial factors (such as transforming growth factor α[TGFα) and (2) γ-aminobutyric acid (GABA)-mediated excitation...
June 2017: Epilepsia
https://www.readbyqxmd.com/read/28589518/forty-years-of-sodium-channels-structure-function-pharmacology-and-epilepsy
#7
William A Catterall
Voltage-gated sodium channels initiate action potentials in brain neurons. In the 1970s, much was known about the function of sodium channels from measurements of ionic currents using the voltage clamp method, but there was no information about the sodium channel molecules themselves. As a postdoctoral fellow and staff scientist at the National Institutes of Health, I developed neurotoxins as molecular probes of sodium channels in cultured neuroblastoma cells. During those years, Bruce Ransom and I crossed paths as members of the laboratories of Marshall Nirenberg and Philip Nelson and shared insights about sodium channels in neuroblastoma cells from my work and electrical excitability and synaptic transmission in cultured spinal cord neurons from Bruce's pioneering electrophysiological studies...
June 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28588450/puzzling-out-synaptic-vesicle-2-family-members-functions
#8
REVIEW
Odile Bartholome, Priscilla Van den Ackerveken, Judit Sánchez Gil, Orianne de la Brassinne Bonardeaux, Pierre Leprince, Rachelle Franzen, Bernard Rogister
Synaptic vesicle proteins 2 (SV2) were discovered in the early 80s, but the clear demonstration that SV2A is the target of efficacious anti-epileptic drugs from the racetam family stimulated efforts to improve understanding of its role in the brain. Many functions have been suggested for SV2 proteins including ions or neurotransmitters transport or priming of SVs. Moreover, several recent studies highlighted the link between SV2 and different neuronal disorders such as epilepsy, Schizophrenia (SCZ), Alzheimer's or Parkinson's disease...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28576733/neuronal-zinc-%C3%AE-2-glycoprotein-is-decreased-in-temporal-lobe-epilepsy-in-patients-and-rats
#9
Ying Liu, Teng Wang, Xi Liu, Xin Wei, Tao Xu, Maojia Yin, Xueying Ding, Lijuan Mo, Lifen Chen
Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein encoded by the AZGP1 gene that is known as a lipid mobilizing factor and is highly homologous to major histocompatibility complex class I family molecules. Recently, transcriptomic research has shown that AZGP1 expression is reduced in the brain tissue of epilepsy patients. However, the cellular distribution and biological role of ZAG in the brain and epilepsy are unclear. Patients with refractory temporal lobe epilepsy (TLE) and brain trauma were included in this study, and pentylenetetrazole (PTZ)-kindled rats were also used...
May 31, 2017: Neuroscience
https://www.readbyqxmd.com/read/28576708/a-systems-level-analysis-of-epileptogenesis-associated-proteome-alterations
#10
Michael Keck, Ganna Androsova, Fabio Gualtieri, Andreas Walker, Eva-Lotta von Rüden, Vera Russmann, Cornelia A Deeg, Stefanie M Hauck, Roland Krause, Heidrun Potschka
Despite intense research efforts, the knowledge about the mechanisms of epileptogenesis and epilepsy is still considered incomplete and limited. However, an in-depth understanding of molecular pathophysiological processes is crucial for the rational selection of innovative biomarkers and target candidates. Here, we subjected proteomic data from different phases of a chronic rat epileptogenesis model to a comprehensive systems level analysis. Weighted Gene Co-expression Network analysis identified several modules of interconnected protein groups reflecting distinct molecular aspects of epileptogenesis in the hippocampus and the parahippocampal cortex...
May 30, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28575153/targeting-oxidative-stress-improves-disease-outcomes-in-a-rat-model-of-acquired-epilepsy
#11
Alberto Pauletti, Gaetano Terrone, Tawfeeq Shekh-Ahmad, Alessia Salamone, Teresa Ravizza, Massimo Rizzi, Anna Pastore, Rosaria Pascente, Li-Ping Liang, Bianca R Villa, Silvia Balosso, Andrey Y Abramov, Erwin A van Vliet, Ennio Del Giudice, Eleonora Aronica, Daniel J Antoine, Manisha Patel, Matthew C Walker, Annamaria Vezzani
Epilepsy therapy is based on antiseizure drugs that treat the symptom, seizures, rather than the disease and are ineffective in up to 30% of patients. There are no treatments for modifying the disease-preventing seizure onset, reducing severity or improving prognosis. Among the potential molecular targets for attaining these unmet therapeutic needs, we focused on oxidative stress since it is a pathophysiological process commonly occurring in experimental epileptogenesis and observed in human epilepsy. Using a rat model of acquired epilepsy induced by electrical status epilepticus, we show that oxidative stress occurs in both neurons and astrocytes during epileptogenesis, as assessed by measuring biochemical and histological markers...
May 30, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28573671/validation-of-reference-genes-for-quantitative-gene-expression-analysis-in-experimental-epilepsy
#12
Chinmaya Sadangi, Felix Rosenow, Braxton A Norwood
To grasp the molecular mechanisms and pathophysiology underlying epilepsy development (epileptogenesis) and epilepsy itself, it is important to understand the gene expression changes that occur during these phases. Quantitative real-time polymerase chain reaction (qPCR) is a technique that rapidly and accurately determines gene expression changes. It is crucial, however, that stable reference genes are selected for each experimental condition to ensure that accurate values are obtained for genes of interest...
June 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28552156/seizures-associated-with-cerebral-arteriovenous-malformations
#13
Johannes Schramm
Various types of seizures and epilepsy are associated with 20-45% of cerebral arteriovenous malformations (AVMs). The necessity to differentiate between occasional seizures, epilepsy with repetitive seizures, and the much rarer drug-resistant epilepsy (DRE) is underlined. It is clear that where there is frequent seizures or DRE, vascular surgeons should take epilepsy surgery aspects into account. The epidemiology of AVM-associated seizures, assumed pathophysiologic mechanisms, most frequent seizures types, and medical treatment are described...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28549652/the-fault-in-their-stars-accumulating-astrocytic-inclusions-associated-with-clusters-of-epileptic-spasms-in-children-with-global-developmental-delay
#14
Robyn Whitney, Sameer AlMehmadi, Bláthnaid McCoy, Ivanna Yau, Ayako Ochi, Hiroshi Otsubo, Shelly K Weiss, James Rutka, Lili-Naz Hazrati, O Carter Snead, Cristina Go
BACKGROUND: The presence of cerebral astrocytic inclusions recently has been described in a subset of children with early-onset refractory epilepsy, with or without structural brain malformations, and varying degrees of developmental delay. METHODS: We describe two new individuals with epilepsy with astrocytic inclusions and suggest that in some children this disorder may represent a unique hemispheric epilepsy. We review previously reported individuals with epilepsy with astrocytic inclusions...
April 18, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28548558/the-role-of-genetic-testing-in-epilepsy-diagnosis-and-management
#15
Yvonne G Weber, Saskia Biskup, Katherine L Helbig, Sarah von Spiczak, Holger Lerche
Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. More than 500 epilepsy-associated genes have been described in the literature. Most of these genes play an important role in neuronal excitability, cortical development or synaptic transmission. A growing number of genetic variations have implications on diagnosis and prognostic or therapeutic advice in terms of a personalized medicine. Area covered: The review presents the different forms of genetic epilepsies with respect to their underlying genetic and functional pathophysiology and aims to give advice for recommended genetic testing...
May 26, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28542864/circadian-clustering-of-spontaneous-epileptic-seizures-emerges-after-pilocarpine-induced-status-epilepticus
#16
Julika Pitsch, Albert J Becker, Susanne Schoch, Johannes Alexander Müller, Marco de Curtis, Vadym Gnatkovsky
OBJECTIVE: Seizures in mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis are thought to develop with various latency intervals after an initial transient brain insult. To study seizure dynamics after an initial transient precipitating insult in a systematic fashion, we utilized continuous video-electroencephalography (EEG) monitoring after the induction of status epilepticus (SE) in a mouse MTLE model. METHODS: Continuous 24/7 video/telemetric hippocampal EEG recordings in the systemic pilocarpine MTLE mouse model...
May 24, 2017: Epilepsia
https://www.readbyqxmd.com/read/28527083/shared-mechanisms-of-epilepsy-migraine-and-affective-disorders
#17
Davide Zarcone, Simona Corbetta
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28503575/association-between-nlpr1-nlpr3-and-p2x7r-gene-polymorphisms-with-partial-seizures
#18
Haidong Wang, Pengfei Xu, Dehua Liao, Ruili Dang, Xin He, Yujin Guo, Pei Jiang
Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28503077/an-unusual-association-of-headache-epilepsy-and-late-onset-kleist-s-pseudodepression-syndrome-in-frontal-lobe-cavernoma-of-the-cerebral-left-hemisphere
#19
Domenico Chirchiglia, Attilio Della Torre, Domenico Murrone, Pasquale Chirchiglia, Rosa Marotta
Cerebral cavernous angioma or cavernoma is a benign vascular malformation, usually asymptomatic. It is infrequent and often its discovery is incidental, a so-called incidentaloma. However, these lesions can be symptomatic, causing headaches, epilepsy, cerebral hemorrhage and other neurological signs depending on the brain area involved. Frontal localization is responsible for psychiatric disorders, particularly the prefrontal region, leading to prefrontal syndrome, a condition common in all frontal lobe tumors...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/28499889/recent-advances-in-epilepsy-genetics
#20
REVIEW
Alessandro Orsini, Federico Zara, Pasquale Striano
In last few years there has been rapid increase in the knowledge of epilepsy genetics. Nowadays, it is estimated that genetic epilepsies include over than 30% of all epilepsy syndromes. Several genetic tests are now available for diagnostic purposes in clinical practice. In particular, next-generation sequencing has proven to be effective in revealing gene mutations causing epilepsies in up to a third of the patients. This has lead also to functional studies that have given insight into disease pathophysiology and consequently to the identification of potential therapeutic targets opening the way of precision medicine for epilepsy patients...
May 9, 2017: Neuroscience Letters
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