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

Toxicologic Pathology ◽

10.1177/01926233211007735 ◽

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.

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Novel crosstalk between ERK MAPK and p38 MAPK leads to homocysteine-NMDA receptor-mediated neuronal cell death

Journal of Neurochemistry ◽

10.1111/jnc.12102 ◽

2012 ◽

Vol 124 (4) ◽

pp. 558-570 ◽

Cited By ~ 38

Author(s):

Ranjana Poddar ◽

Surojit Paul

Keyword(s):

Cell Death ◽

Nmda Receptor ◽

P38 Mapk ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Erk Mapk

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Protective Effects of Active Compounds from Salviae miltiorrhizae Radix against Glutamate-Induced HT-22 Hippocampal Neuronal Cell Death

Processes ◽

10.3390/pr8080914 ◽

2020 ◽

Vol 8 (8) ◽

pp. 914

Author(s):

Hung Manh Phung ◽

Sullim Lee ◽

Ki Sung Kang

Keyword(s):

Cell Death ◽

Rosmarinic Acid ◽

Calcium Influx ◽

Salvia Miltiorrhiza ◽

Neuroprotective Effect ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Salvianolic Acid B ◽

Tanshinone Iia ◽

Salvianolic Acid

Oxidative stress is considered one of the factors that cause dysfunction and damage of neurons, causing diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and Parkinson’s disease (PD).Recently, natural antioxidant sources have emerged as one of the main research areas for the discovery of potential neuroprotectants that can be used to treat neurological diseases. In this research, we assessed the neuroprotective effect of a 70% ethanol Salvia miltiorrhiza Radix (SMR) extract and five of its constituent compounds (tanshinone IIA, caffeic acid, salvianolic acid B, rosmarinic acid, and salvianic acid A) in HT-22 hippocampal cells. The experimental data showed that most samples were effective in attenuating the cytotoxicity caused by glutamate in HT-22 cells, except for rosmarinic acid and salvianolic acid B. Of the compounds tested, tanshinone IIA (TS-IIA) exerted the strongest effect in protecting HT-22 cells against glutamate neurotoxin. Treatment with 400 nM TS-IIA restored HT-22 cell viability almost completely. TS-IIA prevented glutamate-induced oxytosis by abating the accumulation of calcium influx, reactive oxygen species, and phosphorylation of mitogen-activated protein kinases. Moreover, TS-IIA inhibited glutamate-induced cytotoxicity by reducing the activation and phosphorylation of p53, as well as by stimulating Akt expression. This research suggested that TS-IIA is a potential neuroprotective component of SMR, with the ability to protect against neuronal cell death induced by excessive amounts of glutamate.

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Neuroprotective Effects of Propofol in a Model of Ischemic Cortical Cell Cultures

Anesthesiology ◽

10.1097/00000542-200308000-00018 ◽

2003 ◽

Vol 99 (2) ◽

pp. 368-375 ◽

Cited By ~ 65

Author(s):

Lionel J. Velly ◽

Benjamin A. Guillet ◽

Frederique M. Masmejean ◽

André L. Nieoullon ◽

Nicolas J. Bruder ◽

...

Keyword(s):

Lactate Dehydrogenase ◽

Cell Cultures ◽

Glutamate Uptake ◽

Neuroprotective Effect ◽

Glutamate Release ◽

Cortical Cell ◽

Neuroprotective Effects ◽

Mk 801 ◽

Lactate Dehydrogenase Release ◽

Cortical Cell Cultures

Background During cerebral ischemia, excess of glutamate release and dysfunction of its high affinity transport induce an accumulation of extracellular glutamate, which plays an important role in neuronal death. The authors studied the relationship among propofol neuroprotection, glutamate extracellular concentrations, and glutamate transporter activity in a model of ischemic cortical cell cultures. Methods Thirteen-day-old primary cortical neuronal-glial cultures were exposed to a 90-min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber, followed by reoxygenation. Propofol was added only during the OGD period, and its effect was compared to that of the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801). Twenty-four hours after the injury, cell death was quantified by lactate dehydrogenase release and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Extracellular concentrations of glutamate in culture supernatants and glutamate uptake were performed at the end of OGD period by high-performance liquid chromatography and incorporation of l-[3H]glutamate into cells, respectively. Results At clinically relevant concentrations (0.05-10 microm), propofol offered protection equivalent to that of MK-801. It significantly reduced lactate dehydrogenase release and increased the reduction of MTT. At the end of the ischemic injury, propofol was able to reverse the OGD-induced increase in glutamate extracellular concentrations and decrease of glutamate uptake. The inhibition of the glial GLT1 transporter by 3-methyl-glutamate did not further modify the effect of propofol on glutamate uptake, suggesting that GLT1 was not the major target of propofol. Conclusion Propofol showed a neuroprotective effect in this in vitro model of OGD, which was apparently mediated by a GLT1-independent restoration of the glutamate uptake impaired during the injury.

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Neuroprotective effect of Scutellaria baicalensis flavones against global ischemic model in rats

Journal of Nepal Pharmaceutical Association ◽

10.3126/jnpa.v27i1.12144 ◽

2015 ◽

Vol 27 (1) ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Bjakta Prasad Gaire ◽

Young Ock Kim ◽

Zhen Hua Jin ◽

Juyeon Park ◽

Hoyoung Choi ◽

...

Keyword(s):

Cell Death ◽

Gastric Ulcer ◽

Methanol Extract ◽

Biological Effects ◽

Neuroprotective Effect ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Alternative Therapies ◽

Scutellaria Baicalensis ◽

Scutellaria Baicalensis Georgi

Scutellaria baicalensis Georgi (SB) is the medicinal plants mainly used in traditional Chinese medicine. It has been used for the treatment of various chronic inflammatory syndromes including respiratory disease, fever and gastric ulcer in traditional Eastern medicine and its major components; baicalin, baicalein and wogonin; were reported to have various biological effects. The aim of this study was to isolate the neuroprotective flavones from the root of S. baicalensis (SB) by bioactivity-guided fractionation of S. baicalensis methanol extract (SBME). Neuroprotective effect of isolated flavones, namely was studied on global ischemic model in rat by 4-VO. SBME was fractionated with different solvent and resulting fractions were administered at a dose of 25 mg/kg to the rat and potent neuroprotective fractions were sub-fractionated. At a dose of 10 mg/kg, isolated compounds, wogonin, and baicalein inhibited the hippocampal neuronal cell death by 78.6% and 81.0% respectively. Our study suggested that SB and its isolated flavones have potential neuroprotective effect and these findings may be one of the alternative therapies for the management of stroke and other neurodegenerative diseases. DOI: http://dx.doi.org/10.3126/jnpa.v27i1.12144 Journal of Nepal Pharmaceutical Association 2014 Vol.XXVII: 1-8

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Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

Journal of Endocrinology ◽

10.1677/joe-10-0040 ◽

2010 ◽

Vol 205 (3) ◽

pp. 263-270 ◽

Cited By ~ 69

Author(s):

Jiyeon Lee ◽

Eunjin Lim ◽

Yumi Kim ◽

Endan Li ◽

Seungjoon Park

Keyword(s):

Cell Death ◽

Kainic Acid ◽

Hippocampal Neurons ◽

Therapeutic Potential ◽

Excitatory Amino Acid ◽

Neuroprotective Effect ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Proinflammatory Mediators ◽

Hippocampal Neurodegeneration

Ghrelin is an endogenous ligand for GH secretagogue receptor type 1a (GHSR1a), and is produced and released mainly from the stomach. It has been recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. Kainic acid (KA), an excitatory amino acid l-glutamate analog, causes neuronal death in the hippocampus; previous studies suggest that activated microglia and astrocytes actively participate in the pathogenesis of KA-induced hippocampal neurodegeneration. However, it is unclear whether ghrelin has neuroprotective effect in KA-induced hippocampal neurodegeneration. I.p. injection of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of ghrelin significantly attenuated KA-induced neuronal cell death in these regions through the activation of GHSR1a. Ghrelin prevents KA-induced activation of microglia and astrocytes, and the expression of proinflammatory mediators tumor necrosis factor α, interleukin-1β, and cyclooxygenase-2. The inhibitory effect of ghrelin on the activation of microglia and astrocytes appears to be associated with the inhibition of matrix metalloproteinase-3 expression in damaged hippocampal neurons. Our data suggest that ghrelin has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.

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