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Brain damage by epilepsy

Ariana Sherdil, Stéphan Chabardès, Isabelle Guillemain, Sandrine Michallat, Shivadatta Prabhu, Karine Pernet-Gallay, Olivier David, Brigitte Piallat
PURPOSE: Our objective was to propose a new on demand non-human primate model of mesial temporal lobe seizures suitable for pre-clinical innovative therapeutic research. METHODS: Five macaques were stereotaxically implanted unilaterally with a deep recording electrode in the hippocampus. For each experiment, penicillin was injected into the hippocampus and animals were monitored during five consecutive hours. A total of 12-27 experiments with a mean cumulative dose of 162644 ± 70190 UI of penicillin have been performed per animal Injections were repeated at least once a week over a period of 98-276 days...
March 9, 2018: Epilepsy Research
Jinghui Zhang, Nana Qiao, Xiufang Ding, Jiwen Wang
Excitotoxicity and neuronal death following epilepsy involve α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). It forms a protein complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and co-internalizes upon activation of AMPA receptors after epilepsy. Disruption of the GluA2/GAPDH complex with an interfering peptide, TAT-GluA2NT1-3-2, protects cells against AMPAR-mediated excitotoxicity, which have been identified in in-vitro and in-vivo models of brain ischemia. We postulated that disruption of the GluA2/GAPDH interaction with the TAT-GluA2NT1-3-2 peptide would also protect against AMPAR-induced neuronal injury in an in-vivo model of status epilepticus (SE)...
March 21, 2018: Neuroreport
Jaroslava Folbergrová, Pavel Ješina, Hana Kubová, Jakub Otáhal
The presence of oxidative stress in immature brain has been demonstrated during the acute phase of status epilepticus (SE). The knowledge regarding the long periods of survival after SE is not unequivocal, lacking direct evidence. To examine the presence and time profile of oxidative stress, its functional effect on mitochondria and the influence of an antioxidant treatment in immature rats during epileptogenesis, status epilepticus (SE) was induced in immature 12-day-old rats by Li-pilocarpine and at selected periods of the epileptogenesis; rat pups were subjected to examinations...
February 9, 2018: Molecular Neurobiology
Shaunik Sharma, Sreekanth Puttachary, Achala Thippeswamy, Anumantha G Kanthasamy, Thimmasettappa Thippeswamy
Various etiological factors, such as head injury, chemical intoxication, tumors, and gene mutation, can induce epileptogenesis. In animal models, status epilepticus (SE) triggers epileptogenesis. In humans, convulsive SE for >30 min can be a life-threatening medical emergency. The duration and severity of convulsive SE are highly variable in chemoconvulsant animal models. A continuous video-electroencephalography (EEG) recording, and/or diligent direct observation, facilitates quantification of exact duration of different stages of convulsive seizures (Racine stages 3-5) to determine the severity of SE...
2018: Frontiers in Neurology
Ana Gales, Marion Masingue, Stephanie Millecamps, Stephane Giraudier, Laure Grosliere, Claude Adam, Claudio Salim, Vincent Navarro, Yann Nadjar
5,10-Methylene-tetrahydrofolate reductase (MTHFR) deficiency is a genetic disorder that can occur at any age and can be easily detected by increased homocysteinemia. In adolescence/adult onset forms, the clinical picture is often complex with association of various neurological features and thrombosis.Here we report the cases of two adult siblings who experienced focal epilepsy at 18 years old as a first disease manifestation, without other symptom during several years. Upon diagnosis, both patients received metabolic treatment comprising B9, B12 and betaine which has stopped the occurrence of seizures, allowing discontinuation of anti-epileptic drugs...
February 1, 2018: Orphanet Journal of Rare Diseases
Yunbo Shi, Wang Miao, Junfang Teng, Lingli Zhang
BACKGROUND/AIMS: Ginsenoside Rb1 (Rb1) has been reported to have varieties of neuroprotective effects. This study aimed to evaluate the effects of Rb1 on pentylenetetrazol (PTZ)-induced rat brain injury and Mg2+ free-induced neuron injury and analyzed the detailed molecular mechanisms in vivo and in vitro. METHODS: Seizure duration and latency were measured in epilepsy kindled rat. The cognitive impairment was assessed by Morris water maze (MWM) test. Oxidative stress parameters, malondialdehyde (MDA) and glutathione (GSH) were measured by the 2-thiobarbituric acid methods and the DTNB-GSSG reductase recycling methods...
January 22, 2018: Cellular Physiology and Biochemistry
Masahiro Nishibori
High mobility group box-1 (HMGB1), a representative damage-associated molecular patterns (DAMPs), has been reported to be involved in many inflammatory diseases. To validate HMGB1 as a target molecule of inflammatory diseases and to examine the effects of inhibition of HMGB1 on the diseases, we raised anti-HMGB1 monoclonal antibody (mAb) neutralizing extracellular HMGB1 and characterized it. We report the effects of anti-HMGB1 mAb on brain infarction, brain hemorrhage, brain trauma, epilepsy and neuropathic pain using animal models...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
W Quan, Q Xu, F Yang, G H Chen, Z X Lin, Q R Zhang, J H Xiao, G M Lu, Z Q Zhang
Objective: To investigate the damage of gray matter structure in MRI-negative epilepsy patients with different symptoms by voxel-based morphometry (VBM). Methods: From June, 2009 to October, 2016, ninety MRI-negative epilepsy patients and thirty-five healthy volunteers underwent the 3T magnetic resonance imaging scan in Nanjing General Hospital. The patients were divided into three groups, including idiopathic generalized tonic-clonic seizure (I-GTCS), secondarily generalized tonic-clonic seizure (S-GTCS), and partial seizure (PS) according to different symptoms...
December 5, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Qinrui Li, Ying Han, Junbao Du, Hongfang Jin, Jing Zhang, Manman Niu, Jiong Qin
Epilepsy is among the most common neurological disorders. Recurrent seizures result in neuronal death, cognitive deficits and intellectual disabilities in children. Currently, recombinant human erythropoietin (rhEPO) is considered to play a neuroprotective role in nervous system disorders. However, the precise mechanisms through which rhEPO modulates epilepsy remain unknown. Based on results from numerous studies, we hypothesized that rhEPO protects against hippocampal damage in developing rats with seizures probably by modulating autophagy via the ribosomal protein S6 (S6) in a time-dependent manner...
December 13, 2017: Neurochemical Research
Qinrui Li, Ying Han, Junbao Du, Hongfang Jin, Jing Zhang, Manman Niu, Jiong Qin
AIMS: Recurrent seizures can result in neuronal death, cognitive deficits and intellectual disability, which causes devastating damage in children. Recombinant human erythropoietin (rhEPO) is considered a neuroprotective factor in many nervous system diseases. However, the precise mechanisms through which rhEPO exerts its neuroprotective effects on epilepsy remain unknown. Thus, in this study, we determined whether rhEPO protects against brain injury by inducing cortical neuronal autophagy through blunting the mammalian target of rapamycin complex 1 (mTORC1) pathway in the developing brains of rats with seizures...
February 1, 2018: Life Sciences
Francesco Deleo, Maria Thom, Luis Concha, Andrea Bernasconi, Boris C Bernhardt, Neda Bernasconi
Growing evidence highlights the importance of white matter in the pathogenesis of focal epilepsy. Ex vivo and post-mortem studies show pathological changes in epileptic patients in white matter myelination, axonal integrity, and cellular composition. Diffusion-weighted MRI and its analytical extensions, particularly diffusion tensor imaging (DTI), have been the most widely used technique to image the white matter in vivo for the last two decades, and have shown microstructural alterations in multiple tracts both in the vicinity and at distance from the epileptogenic focus...
February 2018: Epilepsy Research
Hye Yeon Nam, Eun Jung Na, Eunyoung Lee, Youngjoo Kwon, Hwa-Jung Kim
Oleamide was first known as a sleep-inducing fatty acid amide, and later shown to have wide range of neuropharmacological effects upon different neurochemical systems. However, the effects of oleamide on brain damage have scarcely been studied, and the molecular mechanisms and sites of its action remain elusive. Kainic acid (KA) has been used to produce an epileptic animal model that mimics human temporal lobe epilepsy and to induce calpain-activated excitotoxicity, which occurs in numerous neurodegenerative disorders...
2017: Frontiers in Pharmacology
Inken Waltl, Christopher Käufer, Sonja Bröer, Chintan Chhatbar, Luca Ghita, Ingo Gerhauser, Muneeb Anjum, Ulrich Kalinke, Wolfgang Löscher
Viral encephalitis is a major risk factor for the development of seizures and epilepsy, but the underlying mechanisms are only poorly understood. Mouse models such as viral encephalitis induced by intracerebral infection with Theiler's virus in C57BL/6 (B6) mice allow advancing our understanding of the immunological and virological aspects of infection-induced seizures and their treatment. Previous studies using the Theiler's virus model in B6 mice have indicated that brain-infiltrating inflammatory macrophages and the cytokines released by these cells are key to the development of acute seizures and hippocampal damage in this model...
February 2018: Neurobiology of Disease
Li-Gang Huang, Jing Zou, Qin-Chi Lu
Temporal lobe epilepsy (TLE) is a chronic neurological disease characterized by recurrent spontaneous seizures. MicroRNAs are dysregulated in various pathological conditions including epilepsy. Therefore, we hypothesized that the dysregulation of these microRNAs might also be associated with the pathogenesis of TLE. In this study, we found that a microRNA, hsa-miR-155-5p, was upregulated in patients with TLE post-surgery, and hence associated with clinical and pathological manifestations and seizure outcomes...
November 27, 2017: Brain Research
Arko Sen, Katherine Gurdziel, Jenney Liu, Wen Qu, Oluwademi O Nuga, Rayanne B Burl, Maik Hüttemann, Roger Pique-Regi, Douglas M Ruden
Traumatic brain injury (TBI) can cause persistent pathological alteration of neurons. This may lead to cognitive dysfunction, depression and increased susceptibility to life threatening diseases, such as epilepsy and Alzheimer's disease. To investigate the underlying genetic and molecular basis of TBI, we subjected w 1118 Drosophila melanogaster to mild closed head trauma and found that mitochondrial activity is reduced in the brains of these flies 24 h after inflicting trauma. To determine the transcriptomic changes after mild TBI, we collected fly heads 24 h after inflicting trauma, and performed RNA-seq analyses...
2017: Frontiers in Genetics
Silvia Colnaghi, Giorgio Beltrami, Guy Poloni, Anna Pichiecchio, Stefano Bastianello, Carlo Andrea Galimberti, Maurizio Versino
Objective: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) may involve extrahippocampal areas of structural damage and dysfunction. The accuracy of medium-term spatial memory can be tested by memory-guided saccades (MGS) to evaluate a functional impairment of the parahippocampal cortex (PHC), while voxel-based morphometry (VBM) analysis can be used to detect a structural damage of the latter region. Methods: MGS with 3- and 30-s memorization delays were compared between 7 patients affected by right MTLE-HS (r-MTLE-HS), 6 patients affected by left MTLE-HS, and 13 healthy controls...
2017: Frontiers in Neurology
Manman Niu, Ying Han, Qinrui Li, Jing Zhang
Epilepsy is among the most common neurological diseases in children. Recurrent seizures can result in hippocampal damage and seriously impair learning and memory functions in children. However, the mechanisms underlying epilepsy-related brain injury are unclear. Neuronal apoptosis is among the most common neuropathological manifestations of brain injury. Endogenous sulfur dioxide (SO2 ) has been shown to be involved in seizures and related neuron apoptosis. However, the role of endogenous SO2 in epilepsy remains unclear...
February 5, 2018: Neuroscience Letters
Antonio Carota, Julien Bogousslavsky
The catastrophic reaction (CR; a disruptive and uncontrolled behavior triggered by anger, irritability, and hostility) and emotionalism (a condition of uncontrolled crying or laughing) are disorders of the emotional regulation and expression, the prevalence of which is underestimated in neurology. Their occurrence is an additional factor of poor outcome for neurologic patients. Although they have been recognized and completely described in their clinical manifestations more than a century ago, many issues remain unsolved regarding their pathogenesis and the respective role of the brain damage and psychological factors...
2018: Frontiers of Neurology and Neuroscience
Shichun Tu, Mohd Waseem Akhtar, Rosa Maria Escorihuela, Alejandro Amador-Arjona, Vivek Swarup, James Parker, Jeffrey D Zaremba, Timothy Holland, Neha Bansal, Daniel R Holohan, Kevin Lopez, Scott D Ryan, Shing Fai Chan, Li Yan, Xiaofei Zhang, Xiayu Huang, Abdullah Sultan, Scott R McKercher, Rajesh Ambasudhan, Huaxi Xu, Yuqiang Wang, Daniel H Geschwind, Amanda J Roberts, Alexey V Terskikh, Robert A Rissman, Eliezer Masliah, Stuart A Lipton, Nobuki Nakanishi
Transcription factor MEF2C regulates multiple genes linked to autism spectrum disorder (ASD), and human MEF2C haploinsufficiency results in ASD, intellectual disability, and epilepsy. However, molecular mechanisms underlying MEF2C haploinsufficiency syndrome remain poorly understood. Here we report that Mef2c+/- (Mef2c-het) mice exhibit behavioral deficits resembling those of human patients. Gene expression analyses on brains from these mice show changes in genes associated with neurogenesis, synapse formation, and neuronal cell death...
November 14, 2017: Nature Communications
Albert J Becker
In many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias (FCDs) and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, i...
November 12, 2017: Neuropathology and Applied Neurobiology
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