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Inflammation epilepsy

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https://www.readbyqxmd.com/read/28427564/inflammation-in-epileptic-encephalopathies
#1
Oleksii Shandra, Solomon L Moshé, Aristea S Galanopoulou
West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28395287/interleukin-1%C3%AE-plays-a-pivotal-role-via-the-pi3k-akt-mtor-signaling-pathway-in-the-chronicity-of-mesial-temporal-lobe-epilepsy
#2
Zhaohua Xiao, Jing Peng, Na Gan, Ahmed Arafat, Fei Yin
OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy. It is often associated with hippocampal sclerosis, which is histopathologically characterized by selective neuron loss, mossy fiber sprouting, and synapse reconstruction, and is the primary cause of refractory epilepsy. Its mechanism has not been fully elucidated. Substantial evidence now supports that inflammatory pathways are activated in epilepsy foci. We have confirmed that the interleukin-1β (IL-1β) level is involved in the epileptogenesis of MTLE, and we further investigated how it works in its chronicity in this study...
April 11, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28389651/unique-residues-in-the-atp-gated-human-p2x7-receptor-define-a-novel-allosteric-binding-pocket-for-the-selective-antagonist-az10606120
#3
Rebecca C Allsopp, Sudad Dayl, Ralf Schmid, Richard J Evans
The P2X7 receptor (P2X7R) for ATP is a therapeutic target for pathophysiological states including inflammation, pain management and epilepsy. This is facilitated by the predicted low side effect profile as the high concentrations of ATP required to activate the receptor are usually only found following cell damage/disease and so P2X7Rs respond to a "danger" signal and are not normally active. AZ10606120 is a selective antagonist for P2X7Rs (IC50 of ~10 nM) and ineffective at the P2X1R (at 10 μM). To determine the molecular basis of selectivity we generated a series of P2X7/1R chimeras and mutants...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386293/long-term-intake-of-uncaria-rhynchophylla-reduces-s100b-and-rage-protein-levels-in-kainic-acid-induced-epileptic-seizures-rats
#4
Nou-Ying Tang, Yi-Wen Lin, Tin-Yun Ho, Chin-Yi Cheng, Chao-Hsiang Chen, Ching-Liang Hsieh
Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p.) and subsequently investigated the effect of Uncaria rhynchophylla (UR) and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28386044/foxp3-exhibits-antiepileptic-effects-in-ictogenesis-involved-in-tlr4-signaling
#5
Fa-Xiang Wang, Xiao-Yi Xiong, Qi Zhong, Zhao-You Meng, Hui Yang, Qing-Wu Yang
Inflammatory processes play critical roles in epileptogenesis but the exact mechanisms that underlie these processes are still not completely understood. In this study, we investigated the role of forkhead transcription factor 3 (Foxp3), a transcription factor that is involved in T-cell differentiation, in epileptogenesis. In both human epileptic tissues and experimental seizure models, we found significant up-regulation of Foxp3 in neurons and glial cells. Of importance, Foxp3(-/-) mice were susceptible to kainic acid-induced seizures, whereas overexpression of Foxp3 reduced acute seizure occurrence and decreased chronic seizure recurrence...
April 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28372497/astrocyte-mediated-inflammation-in-cortical-spreading-depression
#6
Amir Ghaemi, Leila Alizadeh, Shahnaz Babaei, Maryam Jafarian, Maryam Khaleghi Ghadiri, Sven G Meuth, Stjepana Kovac, Ali Gorji
Background Cortical spreading depression (CSD) related diseases such as migraine, cerebrovascular diseases, and epilepsy have been associated with reactive astrocytosis, yet the mechanisms of these tissue changes remain unclear. CSD-induced inflammatory response has been proposed to play a role in some neurological disorders and thus may also contribute to reactive astrocytosis. Methods Using ex vivo brain slices and in vitro astrocytic cultures, we aimed to characterize CSD related changes in astrocytes and markers of inflammation by immunocyto- and immunohistochemistry...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28372486/the-effect-of-il-1%C3%AE-on-synaptophysin-expression-and-electrophysiology-of-hippocampal-neurons-through-the-pi3k-akt-mtor-signaling-pathway-in-a-rat-model-of-mesial-temporal-lobe-epilepsy
#7
Zhaohua Xiao, Jing Peng, Liwen Wu, Ahmed Arafat, Fei Yin
BACKGROUND: The inflammation induced by interleukin-1β (IL-1β) is a critical factor in the pathogenesis of mesial temporal lobe epilepsy (MTLE). Synaptophysin (SYN) and other changes, including neuron electrophysiology, participate in the pathophysiological processes of MTLE. Phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signaling pathway may play a critical role in regulating SYN expression and electrophysiology of hippocampal neurons. METHODS: We used lithium-pilocarpine-treated rats as model of human MTLE, detecting epileptic seizures with digital video-EEG, and evaluating the proteins related to the PI3K/Akt/mTOR signaling pathway by western blot (WB)...
April 4, 2017: Neurological Research
https://www.readbyqxmd.com/read/28360810/brain-infiltration-of-immune-cells-in-caspr2-antibody-associated-mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis
#8
Gökçen Ünverengil, Ebru Nur Vanli Yavuz, Erdem Tüzün, Ece Erdağ, Sevil Kabadayi, Bilge Bilgiç, Betül Baykan
INTRODUCTION: Antibodies directed against neuronal surface antigens have recently been identified in patients with focal temporal lobe epilepsy (TLE) of unknown cause and mesial TLE with hippocampal sclerosis (MTLE-HS), thereby emphasizing the role of autoimmunity in TLE. Antibodies to contactin-associated protein-like 2 (CASPR2) are prevalent in MTLE-HS patients. We aimed to find out whether anti-neuronal autoimmunity might be involved in CASPR2 antibody-related MTLE-HS. METHODS: Surgically resected medial temporal lobe specimens of seropositive and seronegative MTLE-HS patients were examined with hematoxylin and eosin and immunohistochemical staining using specific immune cell markers...
December 2016: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/28352353/anticonvulsant-effect-of-piperine-ameliorates-memory-impairment-inflammation-and-oxidative-stress-in-a-rat-model-of-pilocarpine-induced-epilepsy
#9
Ke Mao, Ding Lei, Heng Zhang, Chao You
The primary active component of black pepper is piperine, which is purified and used to treat epilepsy, achieving higher efficiency when purified. The present study was conducted to evaluate whether the anticonvulsant effect of piperine ameliorates pilocarpine-induced epilepsy, and to investigate the mechanism underlying these effects. Epilepsy was induced in Sprague Dawley rats using pilocarpine. Pilocarpine-induced epilepsy in the rats was treated with 40 mg/kg piperine for 45 consecutive days. Status epilepticus and a Morris water maze test were used to analyze the anticonvulsant effects of piperine in the epileptic rats...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28284836/exciting-and-not-so-exciting-roles-of-pannexins
#10
REVIEW
Eliana Scemes, Jana Velíšková
It is the current view that purinergic signaling regulates many physiological functions. Pannexin1 (Panx1), a member of the gap junction family of proteins is an ATP releasing channel that plays important physio-pathological roles in various tissues, including the CNS. Upon binding to purinergic receptors expressed in neural cells, ATP triggers cellular responses including increased cell proliferation, cell morphology changes, release of cytokines, and regulation of neuronal excitability via release of glutamate, GABA and ATP itself...
March 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28242958/intranasal-delivery-of-mir-146a-mimics-delayed-seizure-onset-in-the-lithium-pilocarpine-mouse-model
#11
Hua Tao, Jianghao Zhao, Tingting Liu, Yujie Cai, Xu Zhou, Huaijie Xing, Yan Wang, Mingkang Yin, Wangtao Zhong, Zhou Liu, Keshen Li, Bin Zhao, Haihong Zhou, Lili Cui
Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28238851/cellular-responses-to-recurrent-pentylenetetrazole-induced-seizures-in-the-adult-zebrafish-brain
#12
Phan Q Duy, Michael A Berberoglu, Christine E Beattie, Charles W Hall
A seizure is a sustained increase in brain electrical activity that can result in loss of consciousness and injury. Understanding how the brain responds to seizures is important for development of new treatment strategies for epilepsy, a neurological condition characterized by recurrent and unprovoked seizures. Pharmacological induction of seizures in rodent models results in a myriad of cellular alterations, including inflammation, angiogenesis, and adult neurogenesis. The purpose of this study is to investigate the cellular responses to recurrent pentylenetetrazole seizures in the adult zebrafish brain...
May 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#13
REVIEW
Beatrice Mihaela Radu, Florin Bogdan Epureanu, Mihai Radu, Paolo Francesco Fabene, Giuseppe Bertini
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i...
March 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28210205/the-atp-gated-p2x7-receptor-as-a-target-for-the-treatment-of-drug-resistant-epilepsy
#14
REVIEW
Edward Beamer, Wolfgang Fischer, Tobias Engel
Despite the progress made in the development of new antiepileptic drugs (AEDs), the biggest challenges that epilepsy presents to drug development have remained unchanged for the last 80 years: finding a treatment with potential for modifying disease progression and reducing the percentage of patients resistant to all pharmacological interventions. The mechanism of action of the majority of AEDs is based on blocking Na(+) and/or Ca(2+) channels, promotion of GABA or inhibition of glutamate signaling. In order for further progress to be made, however, a fuller picture of epilepsy will need to be considered, including changes to blood-brain barrier permeability, synaptic plasticity, network reorganization, and gliosis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28167116/therapeutic-potential-of-an-anti-high-mobility-group-box-1-monoclonal-antibody-in-epilepsy
#15
Junli Zhao, Yi Wang, Cenglin Xu, Keyue Liu, Ying Wang, Liying Chen, Xiaohua Wu, Feng Gao, Yi Guo, Junming Zhu, Shuang Wang, Masahiro Nishibori, Zhong Chen
Brain inflammation is a major factor in epilepsy, and the high mobility group box-1 (HMGB1) protein is known to contribute significantly to the generation of seizures. Here, we investigated the therapeutic potential of an anti-HMGB1 monoclonal antibody (mAb) in epilepsy. anti-HMGB1 mAb attenuated both acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (kainic acid-induced) in a dose-dependent manner. Meanwhile, the anti-HMGB1 mAb also attenuated seizure activities of human brain slices obtained from surgical resection from drug-resistant epilepsy patients...
February 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28135561/focal-cortical-dysplasia-gene-mutations-cell-signaling-and-therapeutic-implications
#16
Philip H Iffland, Peter B Crino
Focal cortical dysplasias (FCDs) are malformations of cortical development (MCDs) that are highly associated with medication-resistant epilepsy and are the most common cause of neocortical epilepsy in children. FCDs are a heterogeneous group of developmental disorders caused by germline or somatic mutations that occur in genes regulating the PI3K/Akt/mTOR pathway-a key pathway in neuronal growth and migration. Accordingly, FCDs are characterized by abnormal cortical lamination, cell morphology (e.g., cytomegaly), and cellular polarity...
January 24, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28127491/sterile-neuroinflammation-and-strategies-for-therapeutic-intervention
#17
REVIEW
Manoj Banjara, Chaitali Ghosh
Sterile neuroinflammation is essential for the proper brain development and tissue repair. However, uncontrolled neuroinflammation plays a major role in the pathogenesis of various disease processes. The endogenous intracellular molecules so called damage-associated molecular patterns or alarmins or damage signals that are released by activated or necrotic cells are thought to play a crucial role in initiating an immune response. Sterile inflammatory response that occurs in Alzheimer's disease (AD), Parkinson's disease (PD), stroke, hemorrhage, epilepsy, or traumatic brain injury (TBI) creates a vicious cycle of unrestrained inflammation, driving progressive neurodegeneration...
2017: International Journal of Inflammation
https://www.readbyqxmd.com/read/28109197/everolimus-is-better-than-rapamycin-in-attenuating-neuroinflammation-in-kainic-acid-induced-seizures
#18
Ming-Tao Yang, Yi-Chin Lin, Whae-Hong Ho, Chao-Lin Liu, Wang-Tso Lee
BACKGROUND: Microglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation. METHODS: In vitro, we treated BV2 cells with KA and LPS...
January 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28087824/neuropathology-of-sudep-role-of-inflammation-blood-brain-barrier-impairment-and-hypoxia
#19
Zuzanna Michalak, Dima Obari, Matthew Ellis, Maria Thom, Sanjay M Sisodiya
OBJECTIVE: To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP. METHODS: Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls...
February 7, 2017: Neurology
https://www.readbyqxmd.com/read/28087439/cerebrovascular-heterogeneity-and-neuronal-excitability
#20
REVIEW
Laura Librizzi, Marco de Curtis, Damir Janigro, Leonie Runtz, Frederic deBock, Emmanuel L Barbier, Nicola Marchi
The cerebral vasculature is a complex tridimensional network of arterial and venous vessels which are anatomically in proximity of and functionally coupled to neurons. Depending on the cellular composition of the vascular wall and its anatomical arrangement, cerebral vessels control regional blood flow, define interstitial homeostasis or cerebrospinal fluid circulation and influence immune cell patrolling. Pathological deviations from these functions promote or are a consequence of brain diseases, directly impacting neuronal firing...
January 10, 2017: Neuroscience Letters
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