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Excitotoxicity

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https://www.readbyqxmd.com/read/29045497/ceftriaxone-and-n-acetylcysteine-induced-brain-tolerance-to-ischemia-influence-on-glutamate-levels-in-focal-cerebral-ischemia
#1
Weronika Krzyżanowska, Bartosz Pomierny, Beata Bystrowska, Lucyna Pomierny-Chamioło, Małgorzata Filip, Bogusława Budziszewska, Joanna Pera
One of the major players in the pathophysiology of cerebral ischemia is disrupted homeostasis of glutamatergic neurotransmission, resulting in elevated extracellular glutamate (Glu) concentrations and excitotoxicity-related cell death. In the brain, Glu concentrations are regulated by Glu transporters, including Glu transporter-1 (GLT-1) and cystine/Glu antiporter (system xc-). Modulation of these transporters by administration of ceftriaxone (CEF, 200 mg/kg, i.p.) or N-acetylcysteine (NAC, 150 mg/kg, i.p.) for 5 days before focal cerebral ischemia may induce brain tolerance to ischemia by significantly limiting stroke-related damage and normalizing Glu concentrations...
2017: PloS One
https://www.readbyqxmd.com/read/29045486/thiamine-deficiency-activates-hypoxia-inducible-factor-1%C3%AE-to-facilitate-pro-apoptotic-responses-in-mouse-primary-astrocytes
#2
Kristy Zera, Jason Zastre
Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD) is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses...
2017: PloS One
https://www.readbyqxmd.com/read/29032009/potential-for-stem-cell-treatment-in-manganism
#3
Thatiane C de Moura, Szeifoul Afadlal, Alan S Hazell
Development of manganism (also known as manganese neurotoxicity) is a major complication of manganese exposure in which neurological dysfunction is linked to accumulation of the metal in brain. Due to neuronal cell death in basal ganglia structures, particularly the globus pallidus, functional recovery is limited. Bearing a resemblance to Parkinson's disease, effective treatment for manganism is currently limited. However, the rapidly developing field of stem cell research offers new hope for the treatment of illnesses in which neurodegeneration is a major feature...
October 11, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29030174/growth-hormone-protects-against-kainate-excitotoxicity-and-induces-bdnf-and-nt3-expression-in-chicken-neuroretinal-cells
#4
C G Martinez-Moreno, T Fleming, M Carranza, J Ávila-Mendoza, M Luna, S Harvey, C Arámburo
There is increasing evidence to suggest a beneficial neuroprotective effect of growth hormone (GH) in the nervous system. While our previous studies have largely focused on retinal ganglion cells (RGCs), we have also found conclusive evidence of a pro-survival effect of GH in cells of the inner nuclear layer (INL) as well as a protective effect on the dendritic trees of the inner plexiform layer (IPL) in the retina. The administration of GH in primary neuroretinal cell cultures protected and induced neural outgrowths...
October 10, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/29030124/targeting-nitric-oxide-and-nmda-receptor-associated-pathways-in-treatment-of-high-grade-glial-tumors-hypotheses-for-nitro-memantine-and-nitrones
#5
REVIEW
Meric A Altinoz, İlhan Elmaci
Glioblastoma multiforme (GBM) is a devastating brain cancer with no curative treatment. Targeting Nitric Oxide (NO) and glutamatergic pathways may help as adjunctive treatments in GBM. NO at low doses promotes tumorigenesis, while at higher levels (above 300 nM) triggers apoptosis. Gliomas actively secrete high amounts of glutamate which activates EGR signaling and mediates degradation of peritumoral tissues via excitotoxic injury. Memantine inhibits NMDA-subtype of glutamate receptors (NMDARs) and induces autophagic death of glioma cells in vitro and blocks glioma growth in vivo...
October 10, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29029261/selective-enhancement-of-domoic-acid-toxicity-in-primary-cultures-of-cerebellar-granule-cells-by-lowering-extracellular-na-concentration
#6
Anabel Pérez-Gómez, David Cabrera-García, Davide Warm, Ann M Marini, Javier Salas Puig, Maria Teresa Fernández-Sánchez, Antonello Novelli
Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was ̴ 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+...
September 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29027929/procyanidin-b2-protects-neurons-from-oxidative-nitrosative-and-excitotoxic-stress
#7
Taylor C Sutcliffe, Aimee N Winter, Noelle C Punessen, Daniel A Linseman
The aberrant generation of oxygen and nitrogen free radicals can cause severe damage to key cellular components, resulting in cell apoptosis. Similarly, excitotoxicity leads to protease activation and mitochondrial dysfunction, which subsequently causes cell death. Each of these factors play critical roles in the neuronal cell death underlying various neurodegenerative diseases. Procyanidin B2 (PB2) is a naturally occurring polyphenolic compound found in high concentrations in cocoa, apples, and grapes. Here, we examine the neuroprotective effects of PB2 in primary cultures of rat cerebellar granule neurons (CGNs) exposed to various stressors...
October 13, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29025157/chronic-pain-after-traumatic-brain-injury-pathophysiology-and-pain-mechanisms
#8
Karen-Amanda Irvine, J David Clark
Background: Traumatic brain injury refers to a broad range of neurological, cognitive, and emotional factors that result from the application of an external force to the head. Individuals recovering from traumatic brain injury will frequently experience acute and chronic pain. Objective: The objective of this paper is to discuss the pathophysiological changes resulting from traumatic brain injury and how these may be involved in the development and persistence of pain after injury...
August 29, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29023772/negative-modulation-of-the-gabaa-%C3%AF-1-receptor-function-by-l-cysteine
#9
Andrea N Beltrán González, Florencia Vicentini, Daniel J Calvo
L-Cysteine is an endogenous Sulphur containing amino acid with multiple and varied roles in the central nervous system, including neuroprotection and the maintenance of the redox balance. However, it was also suggested as an excitotoxic agent implicated in the pathogenesis of neurological disorders such as Parkinson's and Alzheimer's disease. L-Cysteine can modulate the activity of ionic channels, including voltage-gated calcium channels and glutamatergic NMDA receptors, whereas its effects on GABAergic neurotransmission had not been studied before...
October 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29022246/alpha-lipoic-acid-mitigates-toxic-induced-demyelination-in-the-corpus-callosum-by-lessening-of-oxidative-stress-and-stimulation-of-polydendrocytes-proliferation
#10
Nima Sanadgol, Fereshteh Golab, Hassan Askari, Fatemeh Moradi, Marziyeh Ajdary, Mehdi Mehdizadeh
Multiple Sclerosis (MS), is a disease that degenerates myelin in central nervous system (CNS). Reactive oxygen species (ROSs) are toxic metabolites, and accumulating data indicate that ROSs-mediated apoptosis of oligodendrocytes (OLGs) plays a major role in the pathogenesis of MS under oxidative stress conditions. In this study, we investigated the role of endogenous antioxidant alpha-lipoic acid (ALA) as ROSs scavenger in the OLGs loss and myelin degeneration during cuprizone (cup)-induced demyelination in the experimental model of MS...
October 12, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29021742/neuroprotective-mechanisms-of-lycium-barbarum-polysaccharides-against-ischemic-insults-by-regulating-nr2b-and-nr2a-containing-nmda-receptor-signaling-pathways
#11
Zhongshan Shi, Lihui Zhu, Tingting Li, Xiaoya Tang, Yonghui Xiang, Xinjia Han, Luoxing Xia, Ling Zeng, Junhua Nie, Yongxia Huang, Chi Kwan Tsang, Ying Wang, Zhigang Lei, Zaocheng Xu, Kwok-Fai So, Yiwen Ruan
Glutamate excitotoxicity plays an important role in neuronal death after ischemia. However, all clinical trials using glutamate receptor inhibitors have failed. This may be related to the evidence that activation of different subunit of NMDA receptor will induce different effects. Many studies have shown that activation of the intrasynaptic NR2A subunit will stimulate survival signaling pathways, whereas upregulation of extrasynaptic NR2B will trigger apoptotic pathways. A Lycium barbarum polysaccharide (LBP) is a mixed compound extracted from Lycium barbarum fruit...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29017388/pathophysiological-bases-of-comorbidity-tbi-and-ptsd
#12
Gary B Kaplan, Kimberly A Leite-Morris, Lei Wang, Kendra K Rumbika, Stephen C Heinrichs, Xiang Zeng, Liquan Wu, Danielle T Arena, Yang D Teng
The high rates of TBI and PTSD diagnoses encountered in recent years by the U.S. Veterans Affairs Healthcare System have increased public awareness and research investigation into these conditions. In this review, we analyze the neural mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common neuropsychiatric symptoms including anxiety, irritability, insomnia, personality changes and memory problems and this overlap complicates diagnostic differentiation. Interestingly, both TBI and PTSD can be produced by overlapping pathophysiological changes that disrupt neural connections termed the "connectome"...
October 10, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28993512/loss-of-nlrx1-exacerbates-neural-tissue-damage-and-nf-%C3%AE%C2%BAb-signaling-following-brain-injury
#13
Michelle H Theus, Thomas Brickler, Armand L Meza, Sheryl Coutermarsh-Ott, Amanda Hazy, Denis Gris, Irving C Allen
Traumatic and nontraumatic brain injury results from severe disruptions in the cellular microenvironment leading to massive loss of neuronal populations and increased neuroinflammation. The progressive cascade of secondary events, including ischemia, inflammation, excitotoxicity, and free-radical release, contribute to neural tissue damage. NLRX1 is a member of the NLR family of pattern recognition receptors and is a potent negative regulator of several pathways that significantly modulate many of these events...
October 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28993237/sonic-hedgehog-induces-glt-1-degradation-via-pkc-delta-to-suppress-its-transporter-activities
#14
Yuqing Wang, Shanshan Lu, Zhongwei Qu, Lin Wu, Yizheng Wang
GLT-1 is mainly expressed in astrocytes and has a crucial role in glutamate uptake. Sonic hedgehog (SHH) can inhibit glutamate uptake and its pathway is activated in many brain diseases related with glutamate excitotoxicity. However, whether SHH regulates GLT-1 to affect glutamate uptake is not clear. Here, we use pharmacological and genetic methods to show that SHH induces GLT-1 degradation in astrocytes in a manner that is dependent on PKC delta (PKCδ) to regulate GLT-1 activities. GLT-1 protein levels are reduced as early as 2 hs in astrocytes after incubation with SHH, whereas its mRNA levels are not changed...
October 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28992110/nfat3-c4-mediated-excitotoxicity-in-hippocampal-apoptosis-during-radiation-induced-brain-injury
#15
Meiling Xu, Qiuhong Fan, Junjun Zhang, Yanfang Chen, Ruizhe Xu, Liesong Chen, Peifeng Zhao, Ye Tian
Whole brain irradiation (WBI) has become an indispensible tool in the treatment of head and neck cancer, and it has greatly improved patient survival rate and total survival time. In addition, prophylactic cranial irradiation (PCI) has dramatically decreased the incidence of brain metastatic carcinoma. However, WBI may induce temporary functional deficits or even progressive, irreversible cognitive dysfunction that compromises the quality of life for survivors. Unfortunately, the exact molecular mechanisms for cognitive damage remain elusive, and no treatment or preventative measures are available for use in the clinic...
August 10, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28990420/synaptic-activity-protects-neurons-against-calcium-mediated-oxidation-and-contraction-of-mitochondria-during-excitotoxicity
#16
Constanze Depp, Carlos Bas-Orth, Lisa Schroeder, Andrea Hellwig, Hilmar Bading
AIMS: Excitotoxicity triggered by extrasynaptic N-methyl-D-aspartate-type glutamate receptors (NMDARs) has been implicated in many neurodegenerative conditions, including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Mitochondrial calcium overload leading to mitochondrial dysfunction represents an early event in excitotoxicity. Neurons are rendered resistant to excitotoxicity by previous periods of synaptic activity that activates a nuclear calcium-driven neuroprotective gene program...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28987794/the-excitotoxity-of-nmda-receptor-nr2d-subtype-mediates-human-fetal-lung-fibroblasts-proliferation-and-collagen-production
#17
MingJie Wang, ZiQiang Luo, Yinyan Yue, YanRui Wang, Shu Wu, ChuanDing Cao, ZhengChang Liao, XiaoHe Yu, ShaoJie Yue
Studies have suggested that endogenous glutamate and N-methyl-d-aspartate (NMDA) receptor have an excitotoxity role during acute lung injury. Fibroblasts play a critical role in lung development and chronic lung disease after acute lung injury. This study aims to explore the immediate role of NMDAR activation in human lung fibroblasts. The expression of NMDAR 1 subtype (NR1) and four individual NMDAR 2 (NR2) subtypes (NR 2 A to D) was measured in human fetal lung fibroblasts (HFL-1 and MRC-5). Five NMDARs expression were all detectable in two cell lines...
October 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28987401/pm2-5-exposure-stimulates-cox-2-mediated-excitatory-synaptic-transmission-via-ros-nf-%C3%AE%C2%BAb-pathway
#18
Ben Li, Lin Guo, Tingting Ku, Minjun Chen, Guangke Li, Nan Sang
Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the neuroinflammation and synaptic dysfunction, but the mechanisms underlying the process remain unclear. Cyclooxygenase-2 (COX-2) is a key player in neuroinflammation, and has been also implicated in the glutamatergic excitotoxicity and synaptic plasticity. Thus, we hypothesized that COX-2 was involved in PM2.5-promoted neuroinflammation and synaptic dysfunction. Our results revealed that PM2.5 elevated COX-2 expression in primary cultured hippocampal neurons and increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) in hippocampal brain slices...
September 21, 2017: Chemosphere
https://www.readbyqxmd.com/read/28983266/the-psychoanalytic-concept-of-jouissance-and-the-kindling-hypothesis
#19
REVIEW
Yorgos Dimitriadis
This article aims to define the conceptual field of jouissance in Lacanian theory, and put forth the hypothesis of a relationship between certain neurophysiological mechanisms and specific clinical phenomena where jouissance is "kindled" and outside the control of the symbolic process. First, the author briefly introduces Lacan's notion of jouissance and the way it draws on Freud's theorization, and describes the preliminary stages of this conceptual field in Lacan's work. Then, the jouissance related to two other concepts: repetition, with its Freudian and Lacanian nuances, as well as the-exclusively-Lacanian concept of the object petit a...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28982681/early-neonatal-loss-of-inhibitory-synaptic-input-to-the-spinal-motor-neurons-confers-spina-bifida-like-leg-dysfunction-in-a-chicken-model
#20
Md Sakirul Islam Khan, Hiroaki Nabeka, Farzana Islam, Tetsuya Shimokawa, Shouichiro Saito, Xuan Li, Soichiro Kawabe, Fumihiko Hamada, Tetsuya Tachibana, Seiji Matsuda
Spina bifida aperta (SBA), one of the most common congenital malformations, causes lifelong neurological complications particularly in terms of motor dysfunction. Fetuses with SBA exhibit voluntary leg movements in utero and during early neonatal life but these disappear within the first few weeks after birth. However, the pathophysiological sequence underlying such motor dysfunction remains unclear. Additionally, because important insights have yet to be obtained from human cases, an appropriate animal model is essential...
October 5, 2017: Disease Models & Mechanisms
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