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Excitotoxicity

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https://www.readbyqxmd.com/read/28823092/inhibition-of-p2x7-receptors-improves-outcomes-after-traumatic-brain-injury-in-rats
#1
Xiaofeng Liu, Zhengqing Zhao, Ruihua Ji, Jiao Zhu, Qian-Qian Sui, Gillian E Knight, Geoffrey Burnstock, Cheng He, Hongbin Yuan, Zhenghua Xiang
Traumatic brain injury (TBI) is the leading cause of death and disability for people under the age of 45 years worldwide. Neuropathology after TBI is the result of both the immediate impact injury and secondary injury mechanisms. Secondary injury is the result of cascade events, including glutamate excitotoxicity, calcium overloading, free radical generation, and neuroinflammation, ultimately leading to brain cell death. In this study, the P2X7 receptor (P2X7R) was detected predominately in microglia of the cerebral cortex and was up-regulated on microglial cells after TBI...
August 19, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28822104/comparison-of-the-toxic-effects-of-quinolinic-acid-and-3-nitropropionic-acid-in-c-elegans-involvement-of-the-skn-1-pathway
#2
Ilan Kotlar, Aline Colonnello, María Fernanda Aguilera-González, Daiana Silva Avila, María Eduarda de Lima, Rodolfo García-Contreras, Alma Ortíz-Plata, Félix Alexandre Antunes Soares, Michael Aschner, Abel Santamaría
The tryptophan metabolite, quinolinic acid (QUIN), and the mitochondrial toxin 3-nitropropionic acid (3-NP) are two important tools for toxicological research commonly used in neurotoxic models of excitotoxicity, oxidative stress, energy depletion, and neuronal cell death in mammals. However, their toxic properties have yet to be explored in the nematode Caenorhabditis elegans (C. elegans) for the establishment of novel, simpler, complementary, alternative, and predictive neurotoxic model of mammalian neurotoxicity...
August 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28822021/morus-nigra-and-its-major-phenolic-syringic-acid-have-antidepressant-like-and-neuroprotective-effects-in-mice
#3
Ana Paula Dalmagro, Anderson Camargo, Ana Lúcia Bertarello Zeni
Depression is a disorder with a high incidence that has been increasing worldwide although the pathophysiology remains unclear. Moreover, some studies revealed a higher concentration of glutamate and oxidative stress in the patients' brain, which causes cell death by excitotoxicity. Morus nigra L. is known as black mulberry and its leaves are popularly used to treat affections related to menopause, obesity and high cholesterol. M. nigra leaves are a rich fount of phenolics which well-known by the antioxidant property...
August 18, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28821644/calpain-dependent-degradation-of-nucleoporins-contributes-to-motor-neuron-death-in-a-mouse-model-of-chronic-excitotoxicity
#4
Kaori Sugiyama, Tomomi Aida, Masatoshi Nomura, Ryoichi Takayanagi, Hanns U Zeilhofer, Kohichi Tanaka
Glutamate-mediated excitotoxicity induces neuronal death by altering various intracellular signaling pathways and is implicated as a common pathogenic pathway in many neurodegenerative diseases. In the case of motor neuron disease, there is significant evidence to suggest that overactivation of AMPA receptors due to deficiencies in the expression and function of glial glutamate transporter GLT1 and GLAST plays an important role in the mechanisms of neuronal death. However, a causal role for glial glutamate transporter dysfunction in motor neuron death remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28820078/effects-of-excitotoxic-lesion-with-inhaled-anesthetics-on-nervous-system-cells-of-rodents
#5
Maria Fernanda Quiroz Padilla, Gemma Guillazo-Blanch, Magdy Sanchez, Maria Andrea Dominguez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28818695/direct-detection-of-neural-activity-in-vitro-using-magnetic-resonance-electrical-impedance-tomography-mreit
#6
Rosalind J Sadleir, Fanrui Fu, Corey Falgas, Stephen Holland, May Boggess, Samuel C Grant, Eung Je Woo
We describe a sequence of experiments performed in vitro to verify the existence of a new magnetic resonance imaging contrast - Magnetic Resonance Electrical Impedance Tomography (MREIT) -sensitive to changes in active membrane conductivity. We compared standard deviations in MREIT phase data from spontaneously active Aplysia abdominal ganglia in an artificial seawater background solution (ASW) with those found after treatment with an excitotoxic solution (KCl). We found significant increases in MREIT treatment cases, compared to control ganglia subject to extra ASW...
August 14, 2017: NeuroImage
https://www.readbyqxmd.com/read/28817221/neuroprotective-effects-of-honokiol-from-chemistry-to-medicine
#7
REVIEW
Sylwia Talarek, Joanna Listos, Davide Barreca, Ester Tellone, Antoni Sureda, Seyed Fazel Nabavi, Nady Braidy, Seyed Mohammad Nabavi
The incidence of neurological disorders is growing in developed countries together with increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathologies, which make necessary to search for new therapeutic agents. Natural products, most of them used in traditional medicine, are considered promising alternatives for the treatment of neurodegenerative diseases. Honokiol is a natural bioactive phenylpropanoid compound, belonging to the class of neolignan, found in notable amounts in the bark of Magnolia tree, and has been reported to exert diverse pharmacological properties including neuroprotective activities...
August 17, 2017: BioFactors
https://www.readbyqxmd.com/read/28817120/the-erythropoietin-derived-peptide-mk-x-and-erythropoietin-have-neuroprotective-effects-against-ischemic-brain-damage
#8
Seung-Jun Yoo, Bongki Cho, Deokho Lee, Gowoon Son, Yeong-Bae Lee, Hyung Soo Han, Eunjoo Kim, Chanil Moon, Cheil Moon
Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth. Therefore, the development of EPO analogs that would confer neuroprotection without adverse effects has been attempted...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28812276/arundic-acid-increases-expression-and-function-of-astrocytic-glutamate-transporter-eaat1-via-the-erk-akt-and-nf-%C3%AE%C2%BAb-pathways
#9
Pratap Karki, Peter Hong, James Johnson, Edward Pajarillo, Deok-Soo Son, Michael Aschner, Eunsook Y Lee
Glutamate is the major excitatory neurotransmitter in the brain, but excessive synaptic glutamate must be removed to prevent excitotoxic injury and death. Two astrocytic glutamate transporters, excitatory amino acid transporter (EAAT) 1 and 2, play a major role in eliminating excess glutamate from the synapse. Dysregulation of EAAT1 contributes to the pathogenesis of multiple neurological disorders, such as Alzheimer's disease (AD), ataxia, traumatic brain injuries, and glaucoma. In the present study, we investigated the effect of arundic acid on EAAT1 to determine its efficacy in enhancing the expression and function of EAAT1, and its possible mechanisms of action...
August 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28812113/-pathophysiology-of-intracranial-injuries
#10
REVIEW
D Lahner, G Fritsch
Traumatic brain injury (TBI) constitutes a heterogeneous condition that affects the most complex organ of the human body. It is commonly classified by its location as focal injury (e.g. epidural hematoma) and diffuse injury (e.g. diffuse axonal shearing injury) as well as by primary and secondary tissue injury. Accordingly, direct mechanical force causes the primary insult. The tissue damage occurring afterwards is subsumed under the term secondary brain damage. Some of these processes are overlapping and include in the early phase local cerebral ischemia resulting in excitotoxicity, which together with the triggered neuroinflammatory cascade causes the formation of cerebral edema and ultimately increased intracranial pressure once the intracranial compliance is exhausted...
August 15, 2017: Der Unfallchirurg
https://www.readbyqxmd.com/read/28811196/inhibitions-of-pkc-and-camk-ii-synergistically-rescue-ischemia-induced-astrocytic-dysfunction
#11
Zhan Liu, Ying Huang, Lina Liu, Li Zhang
Ischemic neuronal death is presumably caused by glutamate-induced excitotoxicity, in which the increased glutamate release and impaired glutamate reuptake lead to glutamate accumulation. Mechanisms underlying the ischemic deficiency of astrocytic glutamate reuptake remain unclear, which we have studied by analyzing the effect of calmodulin-dependent protein kinase II (CaMK-II) and protein kinase C (PKC) inhibitions on astrocytic glutamate transporter during ischemia. Glutamate transporter current was recorded on the astrocytes in cortical slices...
August 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28811138/intermittent-hypoxia-training-powerful-non-invasive-cerebroprotection-against-ethanol-withdrawal-excitotoxicity
#12
REVIEW
Marianna E Jung, Robert T Mallet
Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca(2+) loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence...
August 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28807794/flavor-and-object-recognition-memory-impairment-induced-by-excitotoxic-lesions-of-the-perirhinal-cortex
#13
E Morillas, B Gómez-Chacón, M Gallo
Recognition memory is based on the ability to assess the familiarity of a previously encountered stimulus. It can be approached using tests for different sensorial modalities. Excitotoxic lesions of the perirhinal cortex (Prh) were performed in order to assess the relevance of its integrity for object and flavor recognition memory. Object recognition memory was impaired with a 24h retention interval. Flavor neophobia attenuation was prevented on a second encounter with the tastant. These results support a role of the perirhinal cortex in mediating the transition from novel to familiar, both in object and flavor recognition memory...
August 12, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28805973/experimental-and-clinical-evidence-of-differential-effects-of-magnesium-sulfate-on-neuroprotection-and-angiogenesis-in-the-fetal-brain
#14
Matthieu Lecuyer, Marina Rubio, Clément Chollat, Maryline Lecointre, Sylvie Jégou, Philippe Leroux, Carine Cleren, Isabelle Leroux-Nicollet, Loic Marpeau, Denis Vivien, Stéphane Marret, Bruno J Gonzalez
Clinical studies showed beneficial effects of magnesium sulfate regarding the risk of cerebral palsy. However, regimen protocols fluctuate worldwide and risks of adverse effects impacting the vascular system have been reported for human neonates, keeping open the question of the optimal dosing. Using clinically relevant concentrations and doses of magnesium sulfate, experiments consisted of characterizing, respectively, ex vivo and in vivo, the effects of magnesium sulfate on the nervous and vascular systems of mouse neonates by targeting neuroprotection, angiogenesis, and hemodynamic factors and in measuring, in human fetuses, the impact of a 4-g neuroprotective loading dose of magnesium sulfate on brain hemodynamic parameters...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28804557/motor-neuron-degeneration-following-glycine-mediated-excitotoxicity-induces-spastic-paralysis-after-spinal-cord-ischemia-reperfusion-injury-in-rabbit
#15
Li Wang, Sen Li, Yuan Liu, Dong-Liang Feng, Long Jiang, Zai-Yun Long, Ya-Min Wu
Spinal cord ischemia and reperfusion (SCIR) injury is the major cause of a wide range of complications, including neural degeneration and devastating paraplegia. Decrease of inhibitory neurotransmitters and increase of excitory neurotransmitters are the major cause for the excitotoxicity of neurons. However, no study has reported the temporal loss of motor neuron in the ventral horn of spinal cord area following SCIR-induced spastic paralysis, not even the mechanism under it. In the present study, we found that the rabbits were mainly spastic paralyzed after spinal cord ischemia-reperfusion injury...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28803438/inhibitor-of-endocannabinoid-deactivation-protects-against-in-vitro-and-in-vivo-neurotoxic-effects-of-paraoxon
#16
Karen L G Farizatto, Sara A McEwan, Vinogran Naidoo, Spyros P Nikas, Vidyanand G Shukla, Michael F Almeida, Aaron Byrd, Heather Romine, David A Karanian, Alexandros Makriyannis, Ben A Bahr
The anticholinesterase paraoxon (Pxn) is related to military nerve agents that increase acetylcholine levels, trigger seizures, and cause excitotoxic damage in the brain. In rat hippocampal slice cultures, high-dose Pxn was applied resulting in a presynaptic vulnerability evidenced by a 64% reduction in synapsin IIb (syn IIb) levels, whereas the postsynaptic protein GluR1 was unchanged. Other signs of Pxn-induced cytotoxicity include the oxidative stress-related production of stable 4-hydroxynonenal (4-HNE)-protein adducts...
August 12, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28797600/the-rat-retrosplenial-cortex-as-a-link-for-frontal-functions-a-lesion-analysis
#17
Anna L Powell, Andrew J D Nelson, Emma Hindley, Moira Davies, John P Aggleton, Seralynne D Vann
Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning...
August 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28796815/effect-of-teriflunomide-on-cortex-basal-ganglia-thalamus-cxbgth-circuit-glutamatergic-dysregulation-in-the-theiler-s-murine-encephalomyelitis-virus-mouse-model-of-multiple-sclerosis
#18
Claire M Modica, Ferdinand Schweser, Michelle L Sudyn, Nicola Bertolino, Marilena Preda, Paul Polak, Danielle M Siebert, Jacqueline C Krawiecki, Michele Sveinsson, Jesper Hagemeier, Michael G Dwyer, Suyog Pol, Robert Zivadinov
BACKGROUND: Pathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors. OBJECTIVES: To investigate the effect of an immunomodulatory therapy (teriflunomide, Aubagio®) on changes of the CxBGTh loop in the Theiler's Murine Encephalomyelitis Virus, (TMEV) mouse model of MS...
2017: PloS One
https://www.readbyqxmd.com/read/28777375/inhibition-of-bcl-xl-prevents-pro-death-actions-of-%C3%AE-n-bcl-xl-at-the-mitochondrial-inner-membrane-during-glutamate-excitotoxicity
#19
Han-A Park, Pawel Licznerski, Nelli Mnatsakanyan, Yulong Niu, Silvio Sacchetti, Jing Wu, Brian M Polster, Kambiz N Alavian, Elizabeth A Jonas
ABT-737 is a pharmacological inhibitor of the anti-apoptotic activity of B-cell lymphoma-extra large (Bcl-xL) protein; it promotes apoptosis of cancer cells by occupying the BH3-binding pocket. We have shown previously that ABT-737 lowers cell metabolic efficiency by inhibiting ATP synthase activity. However, we also found that ABT-737 protects rodent brain from ischemic injury in vivo by inhibiting formation of the pro-apoptotic, cleaved form of Bcl-xL, ΔN-Bcl-xL. We now report that a high concentration of ABT-737 (1 μM), or a more selective Bcl-xL inhibitor WEHI-539 (5 μM) enhances glutamate-induced neurotoxicity while a low concentration of ABT-737 (10 nM) or WEHI-539 (10 nM) is neuroprotective...
August 4, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28777257/chronic-levetiracetam-decreases-hippocampal-and-testicular-aromatase-expression-in-normal-but-not-kainic-acid-induced-experimental-model-of-acute-seizures-in-rats
#20
Mehtap Cincioğlu-Palabiyik, Meral Üner, Dilek Ertoy-Baydar, Yildirim Sara, Hande Karahan, Pelin Kelicen-Uğur
Reproductive disorders are more common in men with epilepsy taking anticonvulsant medications. Antiseizure/anticonvulsant drugs and seizures in medial temporal lobe structures may cause gonadal dysfunction, including infertility, decreased libido, and potency. Levels of circulating bioavailable testosterone are affected by the aromatase enzyme, which converts testosterone into estrogen and may be affected by seizure medications. However, the relationship of anticonvulsant drugs with central aromatase levels is not clear...
August 2, 2017: Neuroreport
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