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Neuroinflammation and epilepsy

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https://www.readbyqxmd.com/read/28950818/inflammation-and-epilepsy-preclinical-findings-and-potential-clinical-translation
#1
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
#2
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
#3
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...
August 30, 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
#4
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
#5
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...
August 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28747388/neuronal-p2x7-receptors-revisited-do-they-really-exist
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28637381/role-of-caspase-3-mediated-apoptosis-in-chronic-caspase-3-cleaved-tau-accumulation-and-blood-brain-barrier-damage-in-the-corpus-callosum-after-traumatic-brain-injury-in-rats
#12
Olena Y Glushakova, Andriy O Glushakov, Cesar V Borlongan, Alex B Valadka, Ronald L Hayes, Alexander V Glushakov
Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421, and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage...
July 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28608235/ferulic-acid-supplementation-for-management-of-depression-in-epilepsy
#13
Tanveer Singh, Taranjot Kaur, Rajesh Kumar Goel
Neuroinflammation driven altered neurochemical milieu have been reported to play a significant role in pathogenesis of comorbid depression in epilepsy. Most of the antiepileptic drugs (AEDs) such as levetiracetam, taigabine, topiramate have not been reported any significant effect in alleviating neuroinflammation, which may explain their ineffectiveness in ameliorating depression associated with epilepsy. The supplementation of antidepressants (ADs) attracts various pharmacokinetic and pharmacodynamic interactions with AEDs and was considered unsafe in epilepsy...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28601603/enhanced-classical-complement-pathway-activation-and-altered-phagocytosis-signaling-molecules-in-human-epilepsy
#14
Season K Wyatt, Thomas Witt, Nicholas M Barbaro, Aaron A Cohen-Gadol, Amy L Brewster
Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about the status of this phenotype in epilepsy. Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in microglia-mediated synaptic pruning. Interestingly, in human and experimental epilepsy, altered mRNA levels of complement molecules were reported. Therefore, to identify a potential role for complement and microglia in the synaptodendritic pathology of epilepsy, we determined the protein levels of classical complement proteins (C1q-C3) along with other phagocytosis signaling molecules in human epilepsy...
September 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28588507/neurovascular-unit-dysfunction-and-blood-brain-barrier-hyperpermeability-contribute-to-schizophrenia-neurobiology-a-theoretical-integration-of-clinical-and-experimental-evidence
#15
REVIEW
Souhel Najjar, Silky Pahlajani, Virginia De Sanctis, Joel N H Stern, Amanda Najjar, Derek Chong
Schizophrenia is a psychotic disorder characterized by delusions, hallucinations, negative symptoms, as well as behavioral and cognitive dysfunction. It is a pathoetiologically heterogeneous disorder involving complex interrelated mechanisms that include oxidative stress and neuroinflammation. Neurovascular endothelial dysfunction and blood-brain barrier (BBB) hyperpermeability are established mechanisms in neurological disorders with comorbid psychiatric symptoms such as epilepsy, traumatic brain injury, and Alzheimer's disease...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28545366/role-of-positron-emission-tomography-for-central-nervous-system-involvement-in-systemic-autoimmune-diseases-status-and-perspectives
#16
Daniele Mauro, Gaetano Barbagallo, Salvatore D'Angelo, Sannino Pasqualina, Saverio Naty, Caterina Bruno, Ignazio Olivieri, Rosa Daniela Grembiale, Francesco Ursini
In the last years, an increasing interest in molecular imaging has been raised by the extending potential of positron emission tomography (PET). The role of PET imaging, originally confined to the oncology setting, is continuously extending thanks to the development of novel radiopharmaceutical and to the implementation of hybrid imaging techniques, where PET scans are combined with computed tomography (CT) or magnetic resonance imaging(MRI) in order to improve spatial resolution. Early preclinical studies suggested that 18F-FDG PET can detect neuroinflammation; new developing radiopharmaceuticals targeting more specifically inflammation-related molecules are moving in this direction...
May 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28527061/ketogenic-diet-in-migraine-rationale-findings-and-perspectives
#17
Piero Barbanti, Luisa Fofi, Cinzia Aurilia, Gabriella Egeo, Massimiliano Caprio
Ketogenic diet (KD) is an established treatment for refractory pediatric epilepsy and a promising therapy for diverse neurological diseases. Clinical data on KD in migraine-obtained from 150 patients investigated in case reports and prospective studies-suggest that KD may be a rapid onset effective prophylaxis for episodic and chronic migraine. KD would contribute to restore brain excitability and metabolism and to counteract neuroinflammation in migraine, although its precise mechanism is still unclear. Randomized controlled studies are needed to confirm the usefulness of KD in migraine and to investigate its optimal duration, repeatability, feasibility in normal weight subjects, efficacy in pediatric population and association to conventional migraine prophylaxis...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28522414/therapeutic-potential-of-agmatine-for-cns-disorders
#18
REVIEW
Vivian B Neis, Priscila B Rosa, Gislaine Olescowicz, Ana Lúcia S Rodrigues
Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders...
September 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28516343/therapeutic-dormancy-to-delay-postsurgical-glioma-recurrence-the-past-present-and-promise-of-focal-hypothermia
#19
REVIEW
Didier Wion
Surgery precedes both radiotherapy and chemotherapy as the first-line therapy for glioma. However, despite multimodal treatment, most glioma patients die from local recurrence in the resection margin. Glioma surgery is inherently lesional, and the response of brain tissue to surgery includes hemostasis, angiogenesis, reactive gliosis and inflammation. Unfortunately, these processes are also associated with tumorigenic side-effects. An increasing amount of evidence indicates that the response to a surgery-related brain injury is hijacked by residual glioma cells and participates in the local regeneration of tumor tissues at the resection margin...
July 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28504645/molecular-isoforms-of-high-mobility-group-box-1-are-mechanistic-biomarkers-for-epilepsy
#20
Lauren Elizabeth Walker, Federica Frigerio, Teresa Ravizza, Emanuele Ricci, Karen Tse, Rosalind E Jenkins, Graeme John Sills, Andrea Jorgensen, Luca Porcu, Thimmasettappa Thippeswamy, Tiina Alapirtti, Jukka Peltola, Martin J Brodie, Brian Kevin Park, Anthony Guy Marson, Daniel James Antoine, Annamaria Vezzani, Munir Pirmohamed
Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance...
June 1, 2017: Journal of Clinical Investigation
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