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Inflammation and epilepsy

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https://www.readbyqxmd.com/read/28284836/exciting-and-not-so-exciting-roles-of-pannexins
#1
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
#2
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
#3
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...
February 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#4
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...
February 9, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28210205/the-atp-gated-p2x7-receptor-as-a-target-for-the-treatment-of-drug-resistant-epilepsy
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28086980/inflammation-in-epileptogenesis-after-traumatic-brain-injury
#12
REVIEW
Kyria M Webster, Mujun Sun, Peter Crack, Terence J O'Brien, Sandy R Shultz, Bridgette D Semple
BACKGROUND: Epilepsy is a common and debilitating consequence of traumatic brain injury (TBI). Seizures contribute to progressive neurodegeneration and poor functional and psychosocial outcomes for TBI survivors, and epilepsy after TBI is often resistant to existing anti-epileptic drugs. The development of post-traumatic epilepsy (PTE) occurs in a complex neurobiological environment characterized by ongoing TBI-induced secondary injury processes. Neuroinflammation is an important secondary injury process, though how it contributes to epileptogenesis, and the development of chronic, spontaneous seizure activity, remains poorly understood...
January 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28074934/disease-modifying-effect-of-intravenous-immunoglobulin-in-an-experimental-model-of-epilepsy
#13
Min Chen, Thiruma V Arumugam, Gayeshika Leanage, Quang M Tieng, Ashwin Yadav, Jeremy F P Ullmann, David T She, Vy Truong, Marc J Ruitenberg, David C Reutens
Novel therapies that prevent or modify the development of epilepsy following an initiating brain insult could significantly reduce the burden of this disease. In light of evidence that immune mechanisms play an important role in generating and maintaining the epileptic condition, we evaluated the effect of a well-established immunomodulatory treatment, intravenous immunoglobulin (IVIg), on the development of epilepsy in an experimental model of epileptogenesis. In separate experiments, IVIg was administered either before (pre-treatment) or after (post-treatment) the onset of pilocarpine status epilepticus (SE)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28060522/aspirin-and-or-omega-3-polyunsaturated-fatty-acids-protect-against-corticohippocampal-neurodegeneration-and-downregulate-lipoxin-a4-production-and-formyl-peptide-receptor-like-1-expression-in-pentylenetetrazole-kindled-rats
#14
Basma A Abd-Elghafour, Norhan M El-Sayed, Amal A M Ahmed, Sawsan A Zaitone, Yasser M Moustafa
There is evidence for a relationship between inflammation and seizures because epilepsy can be caused by or result in inflammation. This study aimed to investigate the effect of aspirin and (or) omega-3 polyunsaturated fatty acids (PUFAs) on seizure activity and neurodegeneration in pentylenetetrazole (PTZ)-kindled rats focusing on their effect on corticohippocampal production of lipoxin A4 (LXA4) and expression of formyl peptide receptor-like 1 (FPRL1) receptors. Male rats were injected with PTZ (35 mg/kg, i...
November 10, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28017800/viral-mouse-models-of-multiple-sclerosis-and-epilepsy-marked-differences-in-neuropathogenesis-following-infection-with-two-naturally-occurring-variants-of-theiler-s-virus-bean-strain
#15
Sonja Bröer, Elias Hage, Christopher Käufer, Ingo Gerhauser, Muneeb Anjum, Lin Li, Wolfgang Baumgärtner, Thomas F Schulz, Wolfgang Löscher
Following intracerebral inoculation, the BeAn 8386 strain of Theiler's virus causes persistent infection and inflammatory demyelinating encephalomyelitis in the spinal cord of T-cell defective SJL/J mice, which is widely used as a model of multiple sclerosis. In contrast, C57BL/6 (B6) mice clear the virus and develop inflammation and lesions in the hippocampus, associated with acute and chronic seizures, representing a novel model of viral encephalitis-induced epilepsy. Here we characterize the geno- and phenotype of two naturally occurring variants of BeAn (BeAn-1 and BeAn-2) that can be used to further understand the viral and host factors involved in the neuropathogenesis in B6 and SJL/J mice...
December 22, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28017648/non-invasive-pet-imaging-of-brain-inflammation-at-disease-onset-predicts-spontaneous-recurrent-seizures-and-reflects-comorbidities
#16
Daniele Bertoglio, Jeroen Verhaeghe, Eva Santermans, Halima Amhaoul, Elisabeth Jonckers, Leonie Wyffels, Annemie Van Der Linden, Niel Hens, Steven Staelens, Stefanie Dedeurwaerdere
Brain inflammation is an important factor in the conversion of a healthy brain into an epileptic one, a phenomenon known as epileptogenesis, offering a new entry point for prognostic tools. The development of anti-epileptogenic therapies to treat before or at disease onset is hampered by our inability to predict the severity of the disease outcome. In a rat model of temporal lobe epilepsy we aimed to assess whether in vivo non-invasive imaging of brain inflammation at disease onset was predictive of spontaneous recurrent seizures (SRS) frequency and severity of depression-like and sensorimotor-related comorbidities...
December 23, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28011391/pathophysiology-of-status-epilepticus
#17
REVIEW
Matthew C Walker
Status epilepticus (SE) is the maximal expression of epilepsy with a high morbidity and mortality. It occurs due to the failure of mechanisms that terminate seizures. Both human and animal data indicate that the longer a seizure lasts, the less likely it is to stop. Recent evidence suggests that there is a critical transition from an ictal to a post-ictal state, associated with a transition from a spatio-temporally desynchronized state to a highly synchronized state, respectively. As SE continues, it becomes progressively resistant to drugs, in particular benzodiazepines due partly to NMDA receptor-dependent internalization of GABA(A) receptors...
December 20, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27988430/kinin-receptors-key-regulators-of-autoimmunity
#18
REVIEW
Rafael Cypriano Dutra
The central function of the immune system is to protect the host from environmental agents such as microbes or chemicals, thereby preserving the integrity of the body, and preventing the onset of illness and infection. Moreover, the immune system is constantly challenged to discriminate self vs. non-self and mediate the correct response, a phenomenon called self-tolerance. The failure of mechanisms responsible for self-tolerance and induction of an immune response against components of the self, induces autoimmunity and culminates however, in several autoimmune diseases...
February 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/27955671/pro-epileptogenic-effects-of-viral-like-inflammation-in-both-mature-and-immature-brains
#19
Nina Dupuis, Andrey Mazarati, Béatrice Desnous, Vibol Chhor, Bobbi Fleiss, Tifenn Le Charpentier, Sophie Lebon, Zsolt Csaba, Pierre Gressens, Pascal Dournaud, Stéphane Auvin
BACKGROUND: Infectious encephalitides are most often associated with acute seizures during the infection period and are risk factors for the development of epilepsy at later times. Mechanisms of viral encephalitis-induced epileptogenesis are poorly understood. Here, we evaluated the contribution of viral encephalitis-associated inflammation to ictogenesis and epileptogenesis using a rapid kindling protocol in rats. In addition, we examined whether minocycline can improve outcomes of viral-like brain inflammation...
December 12, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27918641/evaluation-of-the-biocompatibility-of-polypyrrole-implanted-subdurally-in-gaers
#20
Sebastien H Bauquier, Karen J McLean, Jonathan L Jiang, Ray C Boston, Alan Lai, Zhilian Yue, Simon E Moulton, Amy J Halliday, Gordon Wallace, Mark J Cook
This blinded controlled prospective randomized study investigates the biocompatibility of polypyrrole (PPy) polymer that will be used for intracranial triggered release of anti-epileptic drugs (AEDs). Three by three millimeters PPy are implanted subdurally in six adult female genetic absence epilepsy rats from Strasbourg. Each rat has a polymer implanted on one side of the cortex and a sham craniotomy performed on the other side. After a period of seven weeks, rats are euthanized and parallel series of coronal sections are cut throughout the implant site...
December 5, 2016: Macromolecular Bioscience
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