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Excitotoxicity

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https://www.readbyqxmd.com/read/28634070/high-and-low-concentration-of-17%C3%AE-estradiol-protect-cerebellar-granule-neurons-in-different-time-windows
#1
Irene B Sørvik, Ragnhild E Paulsen
17α-estradiol is a hormonally inactive isomer of 17β-estradiol, but with similar potency as neuroprotector. However, we have previously reported that pretreatment with high concentration (10 μM) of both estrogens abolishes their neuroprotection in rat cerebellar granule neurons. Here, we have examined neuroprotective properties of 17α-estradiol against glutamate-induced excitotoxicity in chicken cerebellar granule neurons using low (1 nM) and high concentration.17α-Estradiol, 1 nM, was neuroprotective when glutamate was administered after a pretreatment period of 24 h, but not when coadministered with glutamate...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629519/erythropoietin-endogenous-protection-of-ischemic-brain
#2
Robert T Mallet, Myoung-Gwi Ryou
The human brain requires uninterrupted delivery of blood-borne oxygen and nutrients to sustain its function. Focal ischemia, particularly, ischemic stroke, and global ischemia imposed by cardiac arrest disrupt the brain's fuel supply. The resultant ATP depletion initiates a complex injury cascade encompassing intracellular Ca(2+) overload, glutamate excitotoxicity, oxido-nitrosative stress, extracellular matrix degradation, and inflammation, culminating in neuronal and astroglial necrosis and apoptosis, neurocognitive deficits, and even death...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28628334/chiral-indolylarylsulfone-non-nucleoside-reverse-transcriptase-inhibitors-as-new-potent-and-broad-spectrum-anti-hiv-1-agents
#3
Valeria Famiglini, Giuseppe La Regina, Antonio Coluccia, Domiziana Masci, Andrea Brancale, Roger Badia, Eva Riveira Muñoz, Jose A Este, Emmanuele Crespan, Alessandro Brambilla, Giovanni Maga, Myriam Catalano, Cristina Limatola, Francesca Romana Romana Formica, Roberto Cirilli, Ettore Novellino, Romano Silvestri
We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8-37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L and K103N-Y181C HIV-1 strains. Six racemic mixtures, 8, 23-25, 31 and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31 and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers...
June 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28627408/developmental-exposure-to-glyphosate-based-herbicide-and-depressive-like-behavior-in-adult-offspring-implication-of-glutamate-excitotoxicity-and-oxidative-stress
#4
Daiane Cattani, Patrícia Acordi Cesconetto, Mauren Kruger Tavares, Eduardo Benedetti Parisotto, Paulo Alexandre De Oliveira, Carla Elise Heinz Rieg, Marina Concli Leite, Rui Daniel Schröder Prediger, Nestor Cubas Wendt, Guilherme Razzera, Danilo Wilhelm Filho, Ariane Zamoner
We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats...
June 13, 2017: Toxicology
https://www.readbyqxmd.com/read/28626499/the-effects-of-blast-exposure-on-protein-deimination-in-the-brain
#5
Peter J Attilio, Michael Flora, Alaa Kamnaksh, Donald J Bradshaw, Denes Agoston, Gregory P Mueller
Oxidative stress and calcium excitotoxicity are hallmarks of traumatic brain injury (TBI). While these early disruptions may be corrected over a relatively short period of time, long-lasting consequences of TBI including impaired cognition and mood imbalances can persist for years, even in the absence of any evidence of overt injury based on neuroimaging. This investigation examined the possibility that disordered protein deimination occurs as a result of TBI and may thus contribute to the long-term pathologies of TBI...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28619002/targeting-astrocytes-for-treatment-in-amyotrophic-lateral-sclerosis
#6
Mina Perić, Dinko Mitrečić, Pavle R Andjus
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder affecting upper and lower motoneurons. The two types, sporadic and familial differ in the aetiopathogenesis but have a similar neuropathology characterized by oxidative stress, excitotoxicity and inflammation. The disease is also characterized by a non-cell autonomous mechanism with astrocytes playing a central role by affecting synaptic glutamate, the blood-brain barrier, and metabolic and trophic support. Two types of therapeutic approaches focusing on astrocytes are presented: a) emerging molecular targets (potassium inward rectifier channels and aquaporins at the astrocyte endfeet, and IP3 receptor signaling pathway), and b) cell therapy with stem cell - generated and transplanted astrocytes...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28617431/nicotine-protects-rat-hypoglossal-motoneurons-from-excitotoxic-death-via-downregulation-of-connexin-36
#7
Silvia Corsini, Maria Tortora, Rossana Rauti, Andrea Nistri
Motoneuron disease including amyotrophic lateral sclerosis may be due, at an early stage, to deficit in the extracellular clearance of the excitatory transmitter glutamate. A model of glutamate-mediated excitotoxic cell death based on pharmacological inhibition of its uptake was used to investigate how activation of neuronal nicotinic receptors by nicotine may protect motoneurons. Hypoglossal motoneurons (HMs) in neonatal rat brainstem slices were exposed to the glutamate uptake blocker DL-threo-β-benzyloxyaspartate (TBOA) that evoked large Ca(2+) transients time locked among nearby HMs, whose number fell by about 30% 4 h later...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28616020/minocycline-targets-multiple-secondary-injury-mechanisms-in-traumatic-spinal-cord-injury
#8
REVIEW
Robert B Shultz, Yinghui Zhong
Minocycline hydrochloride (MH), a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28612917/neonatal-exposure-to-monosodium-glutamate-results-in-dysmorphology-of-orofacial-lower-motor-neurons
#9
Lindsey Foran, Chloe Kupelian, Swati Laroia, Jeffrey Esper, Randy Joseph Kulesza
Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, high levels of extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavor enhancer in many processed foods. Neonatal exposure to MSG has been shown to result in neurodegeneration in several forebrain regions, characterized by neuronal loss and neuroendocrine abnormalities...
June 14, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/28608001/anti-zn-2-toxicity-of-4-hydroxybenzyl-alcohol-in-astrocytes-and-neurons-contribute-to-a-robust-neuroprotective-effects-in-the-postischemic-brain
#10
Lidan Luo, Seung-Woo Kim, Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Ja-Kyeong Lee
4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn(2+) toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects...
June 12, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28606766/medicinal-species-as-mtdls-turnera-diffusa-willd-ex-schult-inhibits-cns-enzymes-and-delays-glutamate-excitotoxicity-in-sh-sy5y-cells-via-oxidative-damage
#11
João Bernardo, Federico Ferreres, Ángel Gil-Izquierdo, Patrícia Valentão, Paula B Andrade
One of the most promising approaches to confront the complexity of central nervous system disorders are new multi-target directed ligands (MTDLs). Five medicinal species (Cereus grandiflorus (L.) Mill., Hyssopus officinalis L., Acorus calamus L., Silybum marianum L. Gaertn. and Turnera diffusa Willd. Ex Schult), selected for their ethnopharmacological relevance, were object for in vitro screening. The aqueous extract of T. diffusa revealed the strongest neuroactive potential, inhibiting monoamine oxidase-A (IC50 = 129...
June 9, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28606040/recent-advances-in-pathophysiology-of-traumatic-brain-injury
#12
Parmeet Kaur, Saurabh Sharma
Traumatic brain injury (TBI) constitutes the primary reason for mortality and morbidity in persons worldwide below 45 years of age. 1.7 million Traumatic events occur yearly in the United States alone, considering for 50,000 deaths. In severe traumatic brain injury sufferers, a considerable achievement attained in treating short-term consequences; but till date, huge failures are occurring in researcher's capability to render severe traumatic brain injury sufferers to an elevated degree of performing. Initial damage force results in Primary brain injury, causing tissue destruction and distortion in the early post-injury period...
June 12, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28605830/sustained-intracellular-acidosis-triggers-the-na-h-exchager-1-activation-in-glutamate-excitotoxicity
#13
Bo Kyung Lee, Yi-Sook Jung
The Na(+)/H(+) exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular H(+) with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-β (PKC-β) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation...
June 14, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28602601/association-of-amine-biomarkers-with-incident-dementia-and-alzheimer-s-disease-in-the-framingham-study
#14
Vincent Chouraki, Sarah R Preis, Qiong Yang, Alexa Beiser, Shuo Li, Martin G Larson, Galit Weinstein, Thomas J Wang, Robert E Gerszten, Ramachandran S Vasan, Sudha Seshadri
INTRODUCTION: The identification of novel biomarkers associated with Alzheimer's disease (AD) could provide key biological insights and permit targeted preclinical prevention. We investigated circulating metabolites associated with incident dementia and AD using metabolomics. METHODS: Plasma levels of 217 metabolites were assessed in 2067 dementia-free Framingham Offspring Cohort participants (mean age = 55.9 ± 9.7 years; 52.4% women). We studied their associations with future dementia and AD risk in multivariate Cox models...
June 8, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28597112/serial-magnetic-resonance-study-in-super-refractory-status-epilepticus-progressive-involvement-of-striatum-and-pallidus-is-a-possible-predictive-marker-of-negative-outcome
#15
Alessandra Ferrari, Paolo Renzetti, Carlo Serrati, Roberto Fancellu
Super refractory status epilepticus (SRSE) is a life-threatening condition in which seizures do not respond to third-line anticonvulsant drug therapy. SRSE is associated with high mortality. How often SRSE occurs, what are the risk factors leading to this condition, and what is the effect on clinical outcome of failure to control seizures are poorly defined. Several studies have evaluated magnetic resonance imaging (MRI) findings in status epilepticus (SE), confirming that SE may directly cause selective neuronal necrosis due to excitotoxic mechanisms, as described in clinical case reports and experimental models...
June 8, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28596976/endogenous-brain-repair-overriding-intrinsic-lineage-determinates-through-injury-induced-micro-environmental-signals
#16
Kathryn S Jones, Bronwen Connor
Adult human neurogenesis has generated excitement over the last 2 decades with the idea that endogenous adult stem cells could act as a potential cell source for brain repair after injury. Indeed, many forms of experimentally induced brain injury including stroke and excitotoxic lesioning can promote proliferation from the subventricular zone and mobilise neuroblasts and oligodendrocyte progenitor cells to migrate through brain parenchyma to damaged regions. However the failure of neuroblasts to mature into appropriate neuronal subtypes for cell replacement has been an issue...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28595944/ido-chronic-immune-activation-and-tryptophan-metabolic-pathway-a-potential-pathophysiological-link-between-depression-and-obesity
#17
REVIEW
Adriano José Maia Chaves Filho, Camila Nayane Carvalho Lima, Silvânia Maria Mendes Vasconcelos, David Freitas de Lucena, Michael Maes, Danielle Macedo
Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs)...
June 5, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28589517/inhibition-of-gap-junction-elevates-glutamate-uptake-in-cultured-astrocytes
#18
Katsura Takano, Masato Ogawa, Kenji Kawabe, Mitsuaki Moriyama, Yoichi Nakamura
Glutamate uptake is a main function of astrocytes to keep extracellular glutamate levels low and protect neurons against glutamate-induced excitotoxicity. On the other hand, astrocyte networks formed by gap junctions, which are consisted with connexins and connecting neighboring cells, are reported to play a critical role in maintaining the homeostasis in the brain. In the present study, we examined the effects of gap junction inhibitors on the glutamate uptake activity in cultured rat cortical astrocytes. At first, we confirmed the effects of gap junction inhibitors, 1-octanol and carbenoxolone, on cell-cell communication by the scrape-loading assay using a fluorescent dye Lucifer yellow...
June 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28586306/revisiting-nicotine-s-role-in-the-ageing-brain-and-cognitive-impairment
#19
Alireza Majdi, Farzin Kamari, Manouchehr Seyedi Vafaee, Saeed Sadigh-Eteghad
Brain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening in age-related changes in diverse molecular pathways leading to pathology...
June 6, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28585865/protein-kinase-c-epsilon-delays-latency-until-anoxic-depolarization-through-arc-expression-and-glur2-internalization
#20
Charles H Cohan, Holly M Stradecki-Cohan, Kahlilia C Morris-Blanco, Nathalie Khoury, Kevin B Koronowski, Mehdi Youbi, Clinton B Wright, Miguel A Perez-Pinzon
Global cerebral ischemia is a debilitating injury that damages the CA1 region of the hippocampus, an area important for learning and memory. Protein kinase C epsilon (PKCɛ) activation is a critical component of many neuroprotective treatments. The ability of PKCɛ activation to regulate AMPA receptors (AMPARs) remains unexplored despite the role of AMPARs in excitotoxicity after brain ischemia. We determined that PKCɛ activation increased expression of a protein linked to learning and memory, activity-regulated cytoskeleton-associated protein (arc)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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