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Neuroinflammation and epilepsy

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https://www.readbyqxmd.com/read/28179120/novel-therapeutic-approaches-for-disease-modification-of-epileptogenesis-for-curing-epilepsy
#1
REVIEW
Bryan L Clossen, Doodipala Samba Reddy
This article describes the recent advances in epileptogenesis and novel therapeutic approaches for the prevention of epilepsy, with a special emphasis on the pharmacological basis of disease-modification of epileptogenesis for curing epilepsy. Here we assess animal studies and human clinical trials of epilepsy spanning 1982-2016. Epilepsy arises from a number of neuronal factors that trigger epileptogenesis, which is the process by which a brain shifts from a normal physiologic state to an epileptic condition...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28127491/sterile-neuroinflammation-and-strategies-for-therapeutic-intervention
#2
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
#3
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/28104433/micrornas-in-the-pathophysiology-of-epilepsy
#4
REVIEW
Gary P Brennan, David C Henshall
Temporal lobe epilepsy is a common and often drug-resistant seizure disorder. The underlying pathological processes which give rise to the development of spontaneous seizures include neuroinflammation, cell loss, neurogenesis and dendritic abnormalities and many of these are driven by insult-induced changes in gene expression and gene expression regulation. MicroRNAs are powerful modulators of post-transcriptional gene expression which are dysregulated during epileptogenesis. The advent of locked nucleic acid (LNA) based inhibitory methods and mimic technology has facilitated in vivo functional assessment of these molecules in epilepsy...
January 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28087250/pharmacology-of-cannabinoids-in-the-treatment-of-epilepsy
#5
REVIEW
Tyler E Gaston, Daniel Friedman
The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use. This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA)...
January 10, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28086980/inflammation-in-epileptogenesis-after-traumatic-brain-injury
#6
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/28061403/berberine-ameliorates-intrahippocampal-kainate-induced-status-epilepticus-and-consequent-epileptogenic-process-in-the-rat-underlying-mechanisms
#7
Reza Sedaghat, Yosra Taab, Zahra Kiasalari, Siamak Afshin-Majd, Tourandokht Baluchnejadmojarad, Mehrdad Roghani
Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27916232/review-neuroinflammation-in-intrauterine-growth-restriction
#8
REVIEW
Julie A Wixey, Kirat K Chand, Paul B Colditz, S Tracey Bjorkman
Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses...
November 25, 2016: Placenta
https://www.readbyqxmd.com/read/27894304/brain-inflammation-is-accompanied-by-peripheral-inflammation-in-cstb-mice-a-model-for-progressive-myoclonus-epilepsy
#9
Olesya Okuneva, Zhilin Li, Inken Körber, Saara Tegelberg, Tarja Joensuu, Li Tian, Anna-Elina Lehesjoki
Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb (-/-) ) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb (-/-) mice in more detail...
November 28, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27884611/microglial-positron-emission-tomography-pet-imaging-in-epilepsy-applications-opportunities-and-pitfalls
#10
Gregory Scott, Mohammad Mahmud, David R Owen, Michael R Johnson
Neuroinflammation is increasingly implicated in epileptogenesis and epilepsy. Microglia are an important mediator of central nervous system inflammation, and the development of positron emission tomography (PET) radioligands which bind the Translocator Protein (TSPO), an outer mitochondrial membrane protein expressed by microglia, has enabled in vivo measurement of neuroinflammation. Here, we outline the principles and potential pitfalls of TSPO PET imaging in relation to epilepsy, and opportunities for using TSPO imaging as a biomarker for future anti-inflammatory based therapeutics in epilepsy...
November 13, 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27836391/diagnosing-and-treating-depression-in-epilepsy
#11
Christian E Elger, Samantha A Johnston, Christian Hoppe
At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal...
October 31, 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27823573/the-sphingosine-1-phosphate-signaling-pathway-in-epilepsy-a-possible-role-for-the-immunomodulator-drug-fingolimod-in-epilepsy-treatment
#12
Antonio Leo, Rita Citraro, Rosario Marra, Ernesto Palma, Eugenio Donato Di Paola, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G protein-coupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis. Magnetic resonance imaging data suggest that fingolimod may be effective in multiple sclerosis MS by preventing blood-brain barrier disruption and brain atrophy...
November 4, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27770579/febrile-infection-related-epilepsy-syndrome-treated-with-anakinra
#13
Daniel L Kenney-Jung, Annamaria Vezzani, Robert J Kahoud, Reghann G LaFrance-Corey, Mai-Lan Ho, Theresa Wampler Muskardin, Elaine C Wirrell, Charles L Howe, Eric T Payne
Febrile infection-related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin-1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super-refractory status epilepticus secondary to FIRES. Anakinra was well tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES...
December 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27761920/isoflurane-prevents-acquired-epilepsy-in-rat-models-of-temporal-lobe-epilepsy
#14
Guy Bar-Klein, Rebecca Klee, Claudia Brandt, Marion Bankstahl, Pablo Bascuñana, Kathrin Töllner, Hotjensa Dalipaj, Jens P Bankstahl, Alon Friedman, Wolfgang Löscher
OBJECTIVE: Acquired epilepsy is a devastating long-term risk of various brain insults, including trauma, stroke, infections, and status epilepticus (SE). There is no preventive treatment for patients at risk. Attributable to the complex alterations involved in epileptogenesis, it is likely that multitargeted approaches are required for epilepsy prevention. We report novel preclinical findings with isoflurane, which exerts various nonanesthetic effects that may be relevant for antiepileptogenesis...
December 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27693857/neuroprotective-mechanism-of-coenzyme-q10-coq10-against-ptz-induced-kindling-and-associated-cognitive-dysfunction-possible-role-of-microglia-inhibition
#15
Manveen Bhardwaj, Anil Kumar
BACKGROUND: Neuroinflammation, oxidative stress and mitochondrial dysfunction play a significant role to explain the pathophysiology of epilepsy. Neuroinflammation through microglia activation has been documented in epileptogenesis. Compounds which inhibit activation of glial cells have been suggested as one of the treatment approaches for the effective treatment of epilepsy. The present study has been designed to investigate the role of coenzyme Q10 and its interaction with minocycline (microglia inhibitor) against pentylenetetrazol (PTZ) induced kindling epilepsy...
December 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27664950/anticonvulsant-and-neuroprotective-effects-of-apelin-13-on-pentylenetetrazole-induced-seizures-in-male-rats
#16
Taj Pari Kalantaripour, Saeed Esmaeili-Mahani, Vahid Sheibani, Majid Asadi-Shekaari, Hamzeh Pasban-Aliabadi
Epilepsy is a common neurological disorder with no effective treatment or cure. Neuropeptide apelin is an endogenous ligand of angiotensin receptor-like 1 (APJ). It has been shown that apelin has protective and anti-neurodegenerative properties. This study was designed to evaluate the effect of apelin-13 on pentylenetetrazole (PTZ)-induced rat model of seizure. Adult male Wistar rats were divided into the experimental groups as follows: control group receiving PTZ; apelin-treated group which received apelin-13 before PTZ; apelin+F13A-treated group which received apelin-13 plus the apelin receptor antagonist (F13A) before PTZ; apelin+naloxone group which received apelin-13+naloxone before PTZ...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27659220/pharmacological-modulation-in-mesial-temporal-lobe-epilepsy-current-status-and-future-perspectives
#17
Antonio Gambardella, Angelo Labate, Pierangelo Cifelli, Gabriele Ruffolo, Laura Mumoli, Eleonora Aronica, Eleonora Palma
Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and genetic components. Recent experimental studies emphasize that drugs or drug combinations that target modulation and circuitry reorganization of the epileptogenic networks favorably modify the complex molecular and cellular alterations underlying MTLE...
September 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27604735/animal-models-of-posttraumatic-seizures-and-epilepsy
#18
Alexander V Glushakov, Olena Y Glushakova, Sylvain Doré, Paul R Carney, Ronald L Hayes
Posttraumatic epilepsy (PTE) is one of the most common and devastating complications of traumatic brain injury (TBI). Currently, the etiopathology and mechanisms of PTE are poorly understood and as a result, there is no effective treatment or means to prevent it. Antiepileptic drugs remain common preventive strategies in the management of TBI to control acute posttraumatic seizures and to prevent the development of PTE, although their efficacy in the latter case is disputed. Different strategies of PTE prophylaxis have been showing promise in preclinical models, but their translation to the clinic still remains elusive due in part to the variability of these models and the fact they do not recapitulate all complex pathologies associated with human TBI...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27601660/infiltrating-monocytes-promote-brain-inflammation-and-exacerbate-neuronal-damage-after-status-epilepticus
#19
Nicholas H Varvel, Jonas J Neher, Andrea Bosch, Wenyi Wang, Richard M Ransohoff, Richard J Miller, Raymond Dingledine
The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27486046/inflammasomes-link-vascular-disease-with-neuroinflammation-and-brain-disorders
#20
REVIEW
Nikolett Lénárt, David Brough, Ádám Dénes
The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer's or Parkinson's disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales...
October 2016: Journal of Cerebral Blood Flow and Metabolism
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