scholarly journals Anesthetic-Induced Oxidative Stress and Potential Protection

2010 ◽  
Vol 10 ◽  
pp. 1473-1482 ◽  
Author(s):  
Cheng Wang ◽  
Xuan Zhang ◽  
Fang Liu ◽  
Merle G. Paule ◽  
William Slikker, Jr.
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Superoxide Dismutase ◽  
Nmda Receptor ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Receptor Subunit ◽  
Nmda Antagonists ◽  
Nmda Receptor Subunit

Prolonged exposure of developing mammals to general anesthetics affects the N-methyl-D-aspartate (NMDA)–type glutamate or γ-aminobutyric acid (GABA) receptor systems and enhances neuronal toxicity. Stimulation of immature neurons by NMDA antagonists or GABA agonists is thought to increase overall nervous system excitability and may contribute to abnormal neuronal cell death during development. Although the precise mechanisms by which NMDA antagonists or GABA agonists cause neuronal cell death are still not completely understood, up-regulation of the NMDA receptor subunit NR1 may be an initiative factor in neuronal cell death. It is increasingly apparent that mitochondria lie at the center of the cell death regulation process. Evidence for the role of oxidative stress in anesthetic-induced neurotoxicity has been generated in studies that apply oxidative stress blockers. Prevention of neuronal death by catalase and superoxide dismutasein vitro, or by M40403 (superoxide dismutase mimetic)in vivo, supports the contention that the involvement of reactive oxygen species (ROS) and the nature of neuronal cell death in rodents is mainly apoptotic. However, more evidence is necessary to in order verify the role of the NMDA receptor subunit NR1 and ROS in anesthetic-induced neurodegeneration.

scholarly journals Role of oxidative stress and caspase 3 in CD47-mediated neuronal cell death

2009 ◽  
Vol 108 (2) ◽  
pp. 430-436 ◽  
Author(s):  
Changhong Xing ◽  
Sunryung Lee ◽  
Woo Jean Kim ◽  
Guang Jin ◽  
Yong-Guang Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell

A novel neuroprotectant PAN-811 protects neurons from oxidative stress

2009 ◽  
Vol 4 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Weiying Pan ◽  
Chanteé Dancik ◽  
Valery Nelson ◽  
Zhi-Gang Jiang ◽  
Michael Lebowitz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Nmda Receptor ◽  
Calcium Influx ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Nmda Receptor Antagonist ◽  
Free Calcium ◽  
Oxygen Species ◽  
Efficient Protection

AbstractHydrogen peroxide (H2O2), a major non-radical reactive oxygen species (ROS) could elicit intracellular oxidative damage and/or cause extracellular free calcium influx by activating the NMDA receptor or through calcium channels. In the present study, NMDA receptor antagonist MK-801 fully blocked H2O2-induced neuronal cell death, whereas green tea (GT) extract containing-antioxidants only partially suppressed the neurotoxicity of H2O2. These suggest that majority of ROS overproduction is downstream of H2O2-induced calcium influx. A novel neuroprotectant PAN-811 was previously demonstrated to efficiently attenuate ischemic neurotoxicity. PAN-811 hereby fully blocks H2O2-elicited neuronal cell death with a more advanced neuroprotective profile than that of GT extract. PAN-811 was also shown to protect against CaCl2-elicited neurotoxicity. Efficient protection against oxidative stress-induced neurotoxicity by PAN-811 indicates its potential application in treatment of ROS-mediated neurodegenerative diseases.

scholarly journals Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by Coenzyme Q10

2005 ◽  
Vol 18 (3) ◽  
pp. 618-627 ◽  
Author(s):  
M. Somayajulu ◽  
S. McCarthy ◽  
M. Hung ◽  
M. Sikorska ◽  
H. Borowy-Borowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Coenzyme Q10 ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hui-Min Yap ◽  
Kwan-Liang Lye ◽  
Loh Teng-Hern Tan
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Monosodium Glutamate ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Glutamate Toxicity ◽  
Extracellular Glutamate

The increased concentration of extracellular glutamate has been reported to play a key role in most of the neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, even though its importance as an amino acid neurotransmitter in mammalian. Glutamate toxicity, which can be caused by excessive intake of monosodium glutamate (MSG), is the major contributor to pathological neuronal cell death. It causes neuronal dysfunction and degeneration in the central nervous system (CNS). Glutamate neurotoxicity can be categorized into two forms, which are receptor-mediated glutamate excitotoxicity and non-receptor mediated glutamate oxidative toxicity. The receptor-mediated glutamate excitotoxicity involved excessive stimulation of glutamate receptors (GluRs) which lead to excessive ion calcium (Ca2+) influx and activates a cell death cascade involving the accumulation of mitochondrially generated reactive oxygen species (ROS). Studies showed excessive extracellular glutamate leads to nerve cell death via the activation of N-methyl-Daspartate (NMDA) receptors in the cases of trauma or stroke. Whereas non-receptor mediated oxidative toxicity involved the breakdown of the cystine/glutamate antiporter (xc - ) mechanism, which leads to the depletion of glutathione (GSH) and causes oxidative stress and cell death. The cystine/glutamate antiporter couples the import of cystine to the export of glutamate. The increased concentration of extracellular glutamate could inhibit the uptake of cystine, which is required for the synthesis of the intracellular antioxidant GSH. GSH plays an important role in the disposal of peroxides by brain cells and in the protection against ROS. Depletion of GSH renders the cell to oxidative stress and ultimately leading to cell death. This article aims to provide a comprehensive review of neurodegenerative diseases and the role of neurotoxin agents, glutamate in these diseases.

Use of Both Fluoro-Jade B and Hematoxylin and Eosin to Detect Cell Death in the Juvenile Rat Brain Exposed to NMDA-Receptor Antagonists or GABA-Receptor Agonists in Safety Assessment

2021 ◽  
pp. 019262332110077
Author(s):  
Catherine A. Picut ◽  
Odete R. Mendes ◽  
David S. Weil ◽  
Sarah Davis ◽  
Cynthia Swanson
Keyword(s):  
Cell Death ◽  
Nmda Receptor ◽  
Rat Brain ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Nmda Receptor Antagonists ◽  
Neonatal Rats ◽  
Receptor Antagonists ◽  
Fluoro Jade B ◽  
Hematoxylin And Eosin

Administration of pediatric anesthetics with N-methyl D-aspartate (NMDA)-receptor antagonist and/or γ-aminobutyric acid (GABA) agonist activities may result in neuronal degeneration and/or neuronal cell death in neonatal rats. Evaluating pediatric drug candidates for this potential neurotoxicity is often part of overall preclinical new drug development strategy. This specialized assessment may require dosing neonatal rats at postnatal day 7 at the peak of the brain growth spurt and evaluating brain tissue 24 to 48 hours following dosing. The need to identify methods to aid in the accurate and reproducible detection of lesions associated with this type of neurotoxic profile is paramount for meeting the changing needs of neuropathology assessment and addressing emerging challenges in the neuroscience field. We document the use of Fluoro-Jade B (FJB) staining, to be used in conjunction with standard hematoxylin and eosin staining, to detect acute neurodegeneration and neuronal cell death that can be caused by some NMDA-receptor antagonists and/or GABA agonists in the neonatal rat brain. The FJB staining is simple, specific, and sensitive and can be performed on brain specimens from the same cohort of animals utilized for standard neurotoxicity assessment, thus satisfying animal welfare recommendations with no effect on achievement of scientific and regulatory goals.

scholarly journals NMDA Receptor-Mediated Neuroprotective Effect of theScutellaria baicalensisGeorgi Extract on the Excitotoxic Neuronal Cell Death in Primary Rat Cortical Cell Cultures

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jinsong Yang ◽  
Xiaohong Wu ◽  
Haogang Yu ◽  
Xinbiao Liao ◽  
Lisong Teng
Keyword(s):  
Cell Death ◽  
Nmda Receptor ◽  
Cell Cultures ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Cortical Cell ◽  
Neuronal Cell ◽  
Ethanol Extract ◽  
Phytochemical Analysis ◽  
Cortical Cell Cultures

The objective of the current research work was to evaluate the neuroprotective effect of the ethanol extract ofScutellaria baicalensis(S.B.) on the excitotoxic neuronal cell death in primary rat cortical cell cultures. The inhibitory effects of the extract were qualitatively and quantitatively estimated by phase-contrast microscopy and lactate dehydrogenase (LDH) assays. The extract exhibited a potent and dose-dependent inhibition of the glutamate-induced excitotoxicity in the culture media. Further, using radioligand binding assays, it was observed that the inhibitory effect of the extract was more potent and selective for the N-methyl-D-aspartate (NMDA) receptor-mediated toxicity. The S.B. ethanol extract competed with [3H] MDL 105,519 for the specific binding to the NMDA receptor glycine site with 50% inhibition occurring at 35.1 μg/mL. Further, NMDA receptor inactivation by the S.B. ethanol extract was concluded from the decreasing binding capability of [3H]MK-801 in the presence of the extract. Thus, S.B. extract exhibited neuroprotection against excitotoxic cell death, and this neuroprotection was mediated through the inhibition of NMDA receptor function by interacting with the glycine binding site of the NMDA receptor. Phytochemical analysis of the bioactive extract revealed the presence of six phytochemical constituents including baicalein, baicalin, wogonin, wogonoside, scutellarin, and Oroxylin A.

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