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Neuroinflammation and epilepsy

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https://www.readbyqxmd.com/read/29651746/human-neural-stem-progenitor-cells-derived-from-epileptic-human-brain-in-a-self-assembling-peptide-nanoscaffold-improve-traumatic-brain-injury-in-rats
#1
Ali Jahanbazi Jahan-Abad, Sajad Sahab Negah, Hassan Hosseini Ravandi, Sedigheh Ghasemi, Maryam Borhani-Haghighi, Walter Stummer, Ali Gorji, Maryam Khaleghi Ghadiri
Traumatic brain injury (TBI) is a disruption in the brain functions following a head trauma. Cell therapy may provide a promising treatment for TBI. Among different cell types, human neural stem cells cultured in self-assembling peptide scaffolds have been suggested as a potential novel method for cell replacement treatment after TBI. In the present study, we accessed the effects of human neural stem/progenitor cells (hNS/PCs) derived from epileptic human brain and human adipose-derived stromal/stem cells (hADSCs) seeded in PuraMatrix hydrogel (PM) on brain function after TBI in an animal model of brain injury...
April 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29644555/a-mechanistic-approach-to-explore-the-neuroprotective-potential-of-zonisamide-in-seizures
#2
Baldeep Kumar, Bikash Medhi, Manish Modi, Biman Saikia, Savita Verma Attri, Ajay Patial
BACKGROUND: Epilepsy, a disease of the brain, is one of the most common serious neurological conditions. It is associated with a group of processes which alter energy metabolism, interrupt cellular ionic homeostasis, cause receptor dysfunction, activate inflammatory cascade, alter neurotransmitter uptake and result in neuronal damage. The increasing knowledge and understanding about the basis of neuronal changes in epilepsy lead to investigate the mechanistic pathway of neuroprotective agents in epilepsy...
April 11, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29593850/systemic-delivery-of-selective-ep1-and-ep3-receptor-antagonists-attenuates-pentylenetetrazole-induced-seizures-in-mice
#3
Cristina R Reschke, Alice B Poersch, Cíntia J Masson, Ana C Jesse, Joseane R Marafiga, Quéli F Lenz, Mauro S Oliveira, David C Henshall, Carlos F Mello
Neuroinflammation plays a major role in brain excitability and may contribute to the development of epilepsy. Prostaglandin E2 (PGE2 ) is a direct mediator of inflammatory responses and, through EP receptors, plays an important role in neuronal excitability. Pharmacological evidence supports that centrally-administered EP1 and EP3 receptor antagonists reduced acutely evoked seizures in rats. Translation of these findings would benefit from evidence of efficacy with a more clinically relevant route of delivery and validation in another species...
2018: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/29590637/the-role-of-the-microrna-146a-complement-factor-h-interleukin-1%C3%AE-mediated-inflammatory-loop-circuit-in-the-perpetuate-inflammation-of-chronic-temporal-lobe-epilepsy
#4
Tao-Ran Li, Yan-Jie Jia, Chao Ma, Wen-Ying Qiu, Qun Wang, Xiao-Qiu Shao, Rui-Juan Lv
Increasing evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the perpetuate inflammation develops. Some recent studies have suggested the possible involvement of microRNA-146a (miR-146a) in the modulation of inflammatory signaling occurring in TLE. To understand how miR-146a modulates inflammatory signaling in TLE, we investigated the role of interleukin-1β (IL-1β), miR-146a and human complement factor H (CFH) in the perpetuate inflammation in rat models of chronic TLE and U251 cells...
March 23, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29566716/overexpression-of-zinc-%C3%AE-2-glycoprotein-suppressed-seizures-and-seizure-related-neuroflammation-in-pentylenetetrazol-kindled-rats
#5
Ying Liu, Teng Wang, Xi Liu, Yuetao Wen, Tao Xu, Xinyuan Yu, Xin Wei, Xueying Ding, Lijuan Mo, Maojia Yin, Xinjie Tan, Lifen Chen
BACKGROUND: Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein reported as an anti-inflammatory adipocytokine. Evidences from clinical and experimental studies revealed that brain inflammation plays important roles in epileptogenesis and seizure. Interestingly, closely relationship between ZAG and many important inflammatory mediators has been proven. Our previous study identified ZAG in neurons and found that ZAG is decreased in epilepsy and interacts with TGFβ and ERK. This study aimed to investigate the role of ZAG in seizure and explore its effect on seizure-related neuroinflammation...
March 22, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29563872/the-metabotropic-purinergic-p2y-receptor-family-as-novel-drug-target-in-epilepsy
#6
REVIEW
Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29506554/effects-of-dexamethasone-on-the-li-pilocarpine-model-of-epilepsy-protection-against-hippocampal-inflammation-and-astrogliosis
#7
Adriana Fernanda K Vizuete, Fernanda Hansen, Elisa Negri, Marina Concli Leite, Diogo Losch de Oliveira, Carlos-Alberto Gonçalves
BACKGROUND: Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy...
March 5, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29468563/neurobiological-correlates-of-alpha-tocopherol-antiepileptogenic-effects-and-microrna-expression-modulation-in-a-rat-model-of-kainate-induced-seizures
#8
Patrizia Ambrogini, Maria Cristina Albertini, Michele Betti, Claudia Galati, Davide Lattanzi, David Savelli, Michael Di Palma, Stefania Saccomanno, Desirée Bartolini, Pierangelo Torquato, Gabriele Ruffolo, Fabiola Olivieri, Francesco Galli, Eleonora Palma, Andrea Minelli, Riccardo Cuppini
Seizure-triggered maladaptive neural plasticity and neuroinflammation occur during the latent period as a key underlying event in epilepsy chronicization. Previously, we showed that α-tocopherol (α-T) reduces hippocampal neuroglial activation and neurodegeneration in the rat model of kainic acid (KA)-induced status epilepticus (SE). These findings allowed us to postulate an antiepileptogenic potential for α-T in hippocampal excitotoxicity, in line with clinical evidence showing that α-T improves seizure control in drug-resistant patients...
February 22, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29464573/intrinsic-inflammation-is-a-potential-anti-epileptogenic-target-in-the-organotypic-hippocampal-slice-model
#9
Seon-Ah Chong, Silvia Balosso, Catherine Vandenplas, Gregory Szczesny, Etienne Hanon, Kasper Claes, Xavier Van Damme, Bénédicte Danis, Jonathan Van Eyll, Christian Wolff, Annamaria Vezzani, Rafal M Kaminski, Isabelle Niespodziany
Understanding the mechanisms of epileptogenesis is essential to develop novel drugs that could prevent or modify the disease. Neuroinflammation has been proposed as a promising target for therapeutic interventions to inhibit the epileptogenic process that evolves from traumatic brain injury. However, it remains unclear whether cytokine-related pathways, particularly TNFα signaling, have a critical role in the development of epilepsy. In this study, we investigated the role of innate inflammation in an in vitro model of post-traumatic epileptogenesis...
February 20, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29454994/epigallocatechin-3-gallate-loaded-pegylated-plga-nanoparticles-a-new-anti-seizure-strategy-for-temporal-lobe-epilepsy
#10
Amanda Cano, Miren Ettcheto, Marta Espina, Carmen Auladell, Ana Cristina Calpena, Jaume Folch, Marta Barenys, Elena Sánchez-López, Antoni Camins, Maria Luisa García
Temporal lobe epilepsy is the most common type of pharmacoresistant epilepsy in adults. Epigallocatechin-3-gallate has aroused much interest because of its multiple therapeutic effects, but its instability compromises the potential effectiveness. PEGylated-PLGA nanoparticles of Epigallocatechin-3-gallate were designed to protect the drug and to increase the brain delivery. Nanoparticles were prepared by the double emulsion method and cytotoxicity, behavioural, Fluoro-Jade C, Iba1 and GFAP immunohistochemistry studies were carried out to determine their effectiveness...
February 15, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29439117/the-pericyte-glia-interface-at-the-blood-brain-barrier
#11
REVIEW
Patrizia Giannoni, Jerome Badaut, Cyril Dargazanli, Alexis Fayd'Herbe De Maudave, Wendy Klement, Vincent Costalat, Nicola Marchi
The cerebrovasculature is a multicellular structure with varying rheological and permeability properties. The outer wall of the brain capillary endothelium is enclosed by pericytes and astrocyte end feet, anatomically assembled to guarantee barrier functions. We, here, focus on the pericyte modifications occurring in disease conditions, reviewing evidence supporting the interplay amongst pericytes, the endothelium, and glial cells in health and pathology. Deconstruction and reactivity of pericytes and glial cells around the capillary endothelium occur in response to traumatic brain injury, epilepsy, and neurodegenerative disorders, impacting vascular permeability and participating in neuroinflammation...
February 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29372545/prospects-of-cannabidiol-for-easing-status-epilepticus-induced-epileptogenesis-and-related-comorbidities
#12
REVIEW
Dinesh Upadhya, Olagide W Castro, Raghavendra Upadhya, Ashok K Shetty
The hippocampus is one of the most susceptible regions in the brain to be distraught with status epilepticus (SE) induced injury. SE can occur from numerous causes and is more frequent in children and the elderly population. Administration of a combination of antiepileptic drugs can abolish acute seizures in most instances of SE but cannot prevent the morbidity typically seen in survivors of SE such as cognitive and mood impairments and spontaneous recurrent seizures. This is primarily due to the inefficiency of antiepileptic drugs to modify the evolution of SE-induced initial precipitating injury into a series of epileptogenic changes followed by a state of chronic epilepsy...
January 25, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29364511/-18-f-ge180-positron-emission-tomographic-imaging-indicates-a-potential-double-hit-insult-in-the-intrahippocampal-kainate-mouse-model-of-temporal-lobe-epilepsy
#13
Mirjam Brackhan, Pablo Bascuñana, Tobias L Ross, Frank M Bengel, Jens P Bankstahl, Marion Bankstahl
OBJECTIVE: Accumulating evidence suggests that brain inflammation, elicited by epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear imaging of brain inflammation in animal models of epileptogenesis represents a diagnostic in vivo approach with potential for direct translation into the clinic. Here, we investigated up-regulation of the translocator protein (TSPO) indicative of microglial activation by serial [18 F]GE180 positron emission tomographic (PET) imaging in a mouse model of temporal lobe epilepsy...
March 2018: Epilepsia
https://www.readbyqxmd.com/read/29356691/the-epileptic-encephalopathy-jungle-from-dr-west-to-the-concepts-of-aetiology-related-and-developmental-encephalopathies
#14
Judith Kalser, J Helen Cross
PURPOSE OF REVIEW: We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy. RECENT FINDINGS: The concept of 'epileptic encephalopathy' has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence...
April 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29346658/potential-for-diet-to-prevent-and-remediate-cognitive-deficits-in-neurological-disorders
#15
Heather M Francis, Richard J Stevenson
The pathophysiology of many neurological disorders involves oxidative stress, neuroinflammation, and mitochondrial dysfunction. There is now substantial evidence that diet can decrease these forms of pathophysiology, and an emerging body of literature relatedly suggests that diet can also prevent or even remediate the cognitive deficits observed in neurological disorders that exhibit such pathology (eg, Alzheimer's disease, multiple sclerosis, age-related cognitive decline, epilepsy). The current review summarizes the emerging evidence in relation to whole diets prominent in the scientific literature-ketogenic, caloric restriction, high polyphenol, and Mediterranean diets-and provides a discussion of the possible underlying neurophysiological mechanisms...
March 1, 2018: Nutrition Reviews
https://www.readbyqxmd.com/read/29329108/cracking-novel-shared-targets-between-epilepsy-and-alzheimer-s-disease-need-of-the-hour
#16
Nitika Garg, Rupa Joshi, Bikash Medhi
Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that seizures are linked with cognitive impairment, and there are various shared etiologies between epilepsy and AD. The connection between hyperexcitability of neurons and cognitive dysfunction in the progression of AD or epileptogenesis plays a vital role for improving selection of treatment for both diseases. Traditionally, seizures occur less frequently and in later stages of age in patients with AD which in turn implies that neurodegeneration causes seizures...
January 12, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29261511/biomechanistic-insights-into-the-roles-of-oxidative-stress-in-generating-complex-neurological-disorders
#17
REVIEW
Mohammad Yusuf, Maria Khan, Majed A Robaian, Riaz A Khan
Neurological diseases like Alzheimer's disease, epilepsy, parkinsonism, depression, Huntington's disease and amyotrophic lateral sclerosis prevailing globally are considered to be deeply influenced by oxidative stress-based changes in the biochemical settings of the organs. The excess oxygen concentration triggers the production of reactive oxygen species, and even the intrinsic antioxidant enzyme system, i.e. SOD, CAT and GSHPx, fails to manage their levels and keep them under desirable limits. This consequently leads to oxidation of protein, lipids and nucleic acids in the brain resulting in apoptosis, proteopathy, proteasomes and mitochondrion dysfunction, glial cell activation as well as neuroinflammation...
March 28, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29246095/role-of-neuroinflammation-in-evolution-of-childhood-epilepsy
#18
Sookyong Koh
Until a decade ago, epilepsy research had focused mainly on alterations of neuronal activities and excitability. Such neurocentric emphasis has neglected the role of glia and involvement of inflammation in the pathogenesis of epilepsy. It is becoming clear that immune and inflammatory reactions do occur in the brain despite the brain's lack of conventional lymphatic drainage and graft acceptance and the presence of vascular brain barrier that tightly regulates infiltration of blood monocytes and lymphocytes...
January 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29230865/glial-source-of-nitric-oxide-in-epileptogenesis-a-target-for-disease-modification-in-epilepsy
#19
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
#20
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 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...
February 2018: Neurobiology of Disease
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