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Neuroinflammation and epilepsy

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https://www.readbyqxmd.com/read/29230865/glial-source-of-nitric-oxide-in-epileptogenesis-a-target-for-disease-modification-in-epilepsy
#1
REVIEW
Shaunik Sharma, Sreekanth Puttachary, Thimmasettappa Thippeswamy
Epileptogenesis is the process of developing an epileptic condition and/or its progression once it is established. The molecules that initiate, promote, and propagate remarkable changes in the brain during epileptogenesis are emerging as targets for prevention/treatment of epilepsy. Epileptogenesis is a continuous process that follows immediately after status epilepticus (SE) in animal models of acquired temporal lobe epilepsy (TLE). Both SE and epileptogenesis are potential therapeutic targets for the discovery of anticonvulsants and antiepileptogenic or disease-modifying agents...
December 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29197620/role-of-the-fyn-pkc%C3%AE-signaling-in-se-induced-neuroinflammation-and-epileptogenesis-in-experimental-models-of-temporal-lobe-epilepsy
#2
Shaunik Sharma, Steven Carlson, Sreekanth Puttachary, Souvarish Sarkar, Lucas Showman, Marson Putra, Anumantha G Kanthasamy, Thimmasettappa Thippeswamy
Status epilepticus (SE) induces neuroinflammation and epileptogenesis, but the mechanisms are not yet fully delineated. The Fyn, a non-receptor Src family of tyrosine kinase (SFK), and its immediate downstream target, PKCδ are emerging as potential mediators of neuroinflammation. In order to first determine the role of Fyn kinase signaling in SE, we tested the efficacy of a SFK inhibitor, saracatinib (25mg/kg, oral) in C57BL/6J mouse kainate model of acute seizures. Saracatinib pretreatment dampened SE severity and completely prevented mortality...
November 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29186698/effect-of-atorvastatin-on-behavioral-alterations-and-neuroinflammation-during-epileptogenesis
#3
Clarissa Vasconcelos de Oliveira, Jéssica Grigoletto, Julia Marion Canzian, Marta Maria Medeiros Frescura Duarte, Thiago Duarte, Ana Flávia Furian, Mauro Schneider Oliveira
Temporal lobe epilepsy (TLE) is the most frequent and medically refractory type of epilepsy in humans. In addition to seizures, patients with TLE suffer from behavioral alterations and cognitive deficits. Poststatus epilepticus model of TLE induced by pilocarpine in rodents has enhanced the understanding of the processes leading to epilepsy and thus, of potential targets for antiepileptogenic therapies. Clinical and experimental evidence suggests that inflammatory processes in the brain may critically contribute to epileptogenesis...
November 26, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29182533/early-gabapentin-treatment-during-the-latency-period-increases-convulsive-threshold-reduces-microglial-activation-and-macrophage-infiltration-in-the-lithium-pilocarpine-model-of-epilepsy
#4
Alicia Rossi, Veronica Murta, Jerónimo Auzmendi, Alberto Javier Ramos
The lithium-pilocarpine model of epilepsy reproduces several features of temporal lobe epilepsy in humans, including the chronological timeline of an initial latency period followed by the development of spontaneous seizures. Epilepsy therapies in humans are implemented, as a rule, after the onset of the spontaneous seizures. We here studied the potential effect on epileptogenesis of starting an early treatment during the latency period, in order to prevent the development of spontaneous seizures. Adult male Wistar rats were treated with 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine...
November 28, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29180982/resveratrol-for-easing-status-epilepticus-induced-brain-injury-inflammation-epileptogenesis-and-cognitive-and-memory-dysfunction-are-we-there-yet
#5
REVIEW
Olagide W Castro, Dinesh Upadhya, Maheedhar Kodali, Ashok K Shetty
Status epilepticus (SE) is a medical emergency exemplified by self-sustaining, unceasing seizures or swiftly recurring seizure events with no recovery between seizures. The early phase after SE event is associated with neurodegeneration, neuroinflammation, and abnormal neurogenesis in the hippocampus though the extent of these changes depends on the severity and duration of seizures. In many instances, over a period, the initial precipitating injury caused by SE leads to temporal lobe epilepsy (TLE), typified by spontaneous recurrent seizures, cognitive, memory and mood impairments associated with chronic inflammation, reduced neurogenesis, abnormal synaptic reorganization, and multiple molecular changes in the hippocampus...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29153613/brain-expression-of-inflammatory-mediators-in-mesial-temporal-lobe-epilepsy-patients
#6
Bárbara Leal, João Chaves, Cláudia Carvalho, Rui Rangel, Agostinho Santos, Andreia Bettencourt, João Lopes, João Ramalheira, Berta M Silva, António Martins da Silva, Paulo P Costa
Neuroinflammation may be central in epileptogenesis. In this study we analysed inflammatory reaction markers in brain tissue of Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) patients. TLR4, IL-1β and IL-10 gene expression as well as the presence of activated HLA-DR+ microglia was evaluated in 23 patients and 10 cadaveric controls. Inflammation characterized by the presence of HLA-DR(+) microglia and TLR4, IL-1β overexpression was evident in hippocampus and anterior temporal cortex of MTLE-HS patients...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29066951/connexin43-and-pannexin-based-channels-in-neuroinflammation-and-cerebral-neuropathies
#7
REVIEW
Denis Sarrouilhe, Catherine Dejean, Marc Mesnil
Connexins (Cx) are largely represented in the central nervous system (CNS) with 11 Cx isoforms forming intercellular channels. Moreover, in the CNS, Cx43 can form hemichannels (HCs) at non-junctional membrane as does the related channel-forming Pannexin1 (Panx1) and Panx2. Opening of Panx1 channels and Cx43 HCs appears to be involved in inflammation and has been documented in various CNS pathologies. Over recent years, evidence has accumulated supporting a link between inflammation and cerebral neuropathies (migraine, Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder, autism spectrum disorder (ASD), epilepsy, schizophrenia, bipolar disorder)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29049053/treatment-options-for-posttraumatic-epilepsy
#8
Lara L Zimmermann, Ryan M Martin, Fady Girgis
PURPOSE OF REVIEW: Posttraumatic seizures (PTS) and posttraumatic epilepsy (PTE) are common and debilitating consequences of traumatic brain injury (TBI). Early PTS result in secondary brain injury by raising intracranial pressure and worsening cerebral edema and metabolic crisis. PTE is a localization-related epilepsy strongly associated with TBI severity, but risk factors for PTE and epileptogenesis are incompletely understood and are active areas of research. Medical management of PTS in adults and children is reviewed...
December 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29031614/high-mobility-group-box-1-is-a-novel-pathogenic-factor-and-a-mechanistic-biomarker-for-epilepsy
#9
Teresa Ravizza, Gaetano Terrone, Alessia Salamone, Federica Frigerio, Silvia Balosso, Daniel J Antoine, Annamaria Vezzani
Approximately 30% of epilepsy patients experience seizures that are not controlled by the available drugs. Moreover, these drugs provide mainly a symptomatic treatment since they do not interfere with the disease's mechanisms. A mechanistic approach to the discovery of key pathogenic brain modifications causing seizure onset, recurrence and progression is instrumental for designing novel and rationale therapeutic interventions that could modify the disease course or prevent its development. In this regard, increasing evidence shows that neuroinflammation is a pathogenic factor in drug-resistant epilepsies...
October 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28950818/inflammation-and-epilepsy-preclinical-findings-and-potential-clinical-translation
#10
Gaetano Terrone, Alessia Salamone, Annamaria Vezzani
BACKGROUND: The lack of treatments which can prevent epilepsy development or improve disease prognosis represents an unmet and urgent clinical need. The development of such drugs requires a deep understanding of the mechanisms underlying disease pathogenesis. In the last decade, preclinical studies in models of acute seizures and of chronic epilepsy highlighted that neuroinflammation arising in brain areas of seizure onset and generalization is a key contributor to neuronal hyper-excitability underlying seizure generation...
September 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28942474/svct2-expression-and-function-in-reactive-astrocytes-is-a-common-event-in-different-brain-pathologies
#11
Katterine Salazar, Fernando Martínez, Margarita Pérez-Martín, Manuel Cifuentes, Laura Trigueros, Luciano Ferrada, Francisca Espinoza, Natalia Saldivia, Romina Bertinat, Katherine Forman, María José Oviedo, Antonio J López-Gambero, Christian Bonansco, Ernesto R Bongarzone, Francisco Nualart
Ascorbic acid (AA), the reduced form of vitamin C, acts as a neuroprotector by eliminating free radicals in the brain. Sodium/vitamin C co-transporter isoform 2 (SVCT2) mediates uptake of AA by neurons. It has been reported that SVCT2 mRNA is induced in astrocytes under ischemic damage, suggesting that its expression is enhanced in pathological conditions. However, it remains to be established if SVCT expression is altered in the presence of reactive astrogliosis generated by different brain pathologies. In the present work, we demonstrate that SVCT2 expression is increased in astrocytes present at sites of neuroinflammation induced by intracerebroventricular injection of a GFP-adenovirus or the microbial enzyme, neuraminidase...
September 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28856625/inhibition-of-p2x7-receptor-ameliorates-nuclear-factor-kappa-b-mediated-neuroinflammation-induced-by-status-epilepticus-in-rat-hippocampus
#12
Cheng Huang, Xiao-Sa Chi, Rui Li, Xin Hu, Hai-Xia Xu, Jin-Mei Li, Dong Zhou
P2X7 receptor (P2X7R) has been reported participating in neuroinflammation in multiple neurological diseases. We explored the role of P2X7R in a rat status epilepticus (SE) model induced by coriaria lactone (CL) and its association with neuroinflammation. Thirty minutes after intracerebroventricular infusion with P2X7R antagonists Brilliant blue G (BBG), A-438079, A-740003, or agonists 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), SE was induced by intramuscular injection of CL in Sprague-Dawley rats...
October 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28831096/inflammatory-cytokine-induced-changes-in-neural-network-activity-measured-by-waveform-analysis-of-high-content-calcium-imaging-in-murine-cortical-neurons
#13
Benjamin D S Clarkson, Robert J Kahoud, Christina B McCarthy, Charles L Howe
During acute neuroinflammation, increased levels of cytokines within the brain may contribute to synaptic reorganization that results in long-term changes in network hyperexcitability. Indeed, inflammatory cytokines are implicated in synaptic dysfunction in epilepsy and in an array of degenerative and autoimmune diseases of the central nervous system. Current tools for studying the impact of inflammatory factors on neural networks are either insufficiently fast and sensitive or require complicated and costly experimental rigs...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822838/scavenging-reactive-oxygen-species-inhibits-status-epilepticus-induced-neuroinflammation
#14
Pallavi B McElroy, Li-Ping Liang, Brian J Day, Manisha Patel
Inflammation has been identified as an important mediator of seizures and epileptogenesis. Understanding the mechanisms underlying seizure-induced neuroinflammation could lead to the development of novel therapies for the epilepsies. Reactive oxygen species (ROS) are recognized as mediators of seizure-induced neuronal damage and are known to increase in models of epilepsies. ROS are also known to contribute to inflammation in several disease states. We hypothesized that ROS are key modulators of neuroinflammation i...
December 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28747388/neuronal-p2x7-receptors-revisited-do-they-really-exist
#15
REVIEW
Peter Illes, Tahir Muhammad Khan, Patrizia Rubini
P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic receptors (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long intracellular C terminus regulating trafficking to the cell membrane, protein-protein interactions, and post-translational modification. Their C-terminal tail is especially important in enabling the transition from the nonselective ion channel mode to a membrane pore allowing the passage of large molecules. There is an ongoing dispute on the existence of neuronal P2X7Rs with consequences for our knowledge on their involvement in neuroinflammation, aggravating stroke, temporal lobe epilepsy, neuropathic pain, and various neurodegenerative diseases...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28716963/chemokine-ccl2-ccr2-signaling-induces-neuronal-cell-death-via-stat3-activation-and-il-1%C3%AE-production-after-status-epilepticus
#16
Dai-Shi Tian, Jiyun Peng, Madhuvika Murugan, Li-Jie Feng, Jun-Li Liu, Ukpong B Eyo, Li-Jun Zhou, Rochelle Mogilevsky, Wei Wang, Long-Jun Wu
Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1 d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1(GFP/+):CCR2(RFP/+) double-transgenic mice, we demonstrated that CCL2-CCR2 signaling has a role in resident microglial activation and blood-derived monocyte infiltration...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28677172/neurological-and-psychiatric-associations-in-bullous-pemphigoid-more-than-skin-deep
#17
REVIEW
Anna-Kaisa Försti, Laura Huilaja, Enno Schmidt, Kaisa Tasanen
In elderly patients, bullous pemphigoid (BP) is associated with several comorbidities; the strongest association occurs between BP and neurological diseases. Different types of dementia, Parkinson's disease, cerebrovascular disorders and epilepsy all have a significant association with BP, but patients with multiple sclerosis have the highest risk of BP. An existing neurological disorder appears to increase the risk for subsequent BP, but an increased risk for developing some neurological diseases has also been reported following BP diagnosis...
July 4, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28675560/neuroinflammation-imaging-markers-for-epileptogenesis
#18
Matthias J Koepp, Eric Årstad, Jens P Bankstahl, Stefanie Dedeurwaerdere, Alon Friedman, Heidrun Potschka, Teresa Ravizza, William H Theodore, Tallie Z Baram
Epilepsy can be a devastating disorder. In addition to debilitating seizures, epilepsy can cause cognitive and emotional problems with reduced quality of life. Therefore, the major aim is to prevent the disorder in the first place: identify, detect, and reverse the processes responsible for its onset, and monitor and treat its progression. Epilepsy often occurs following a latent period of months to years (epileptogenesis) as a consequence of a brain insult, such as head trauma, stroke, or status epilepticus...
July 2017: Epilepsia
https://www.readbyqxmd.com/read/28675559/neuroinflammation-in-epileptogenesis-insights-and-translational-perspectives-from-new-models-of-epilepsy
#19
Melissa L Barker-Haliski, Wolfgang Löscher, H Steve White, Aristea S Galanopoulou
Animal models have provided a wealth of information on mechanisms of epileptogenesis and comorbidogenesis, and have significantly advanced our ability to investigate the potential of new therapies. Processes implicating brain inflammation have been increasingly observed in epilepsy research. Herein we discuss the progress on animal models of epilepsy and comorbidities that inform us on the potential role of inflammation in epileptogenesis and comorbidity pathogenesis in rodent models of West syndrome and the Theiler's murine encephalomyelitis virus (TMEV) mouse model of viral encephalitis-induced epilepsy...
July 2017: Epilepsia
https://www.readbyqxmd.com/read/28675059/immunogenetic-predisposing-factors-for-mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis
#20
Bárbara Leal, João Chaves, Cláudia Carvalho, Andreia Bettencourt, Cláudia Brito, Daniela Boleixa, Joel Freitas, Sandra Brás, João Lopes, João Ramalheira, Paulo P Costa, Berta Martins da Silva, António Martins da Silva
PURPOSE: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1β and TNF-α, in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with Febrile Seizures (FS) and MTLE-HS development. The Human Leukocyte Antigen (HLA) system has also been implicated in diverse epileptic entities suggesting a variable role of this system in epilepsy...
July 4, 2017: International Journal of Neuroscience
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