Neuroprotective Effects of Cactus Polysaccharide on Oxygen and Glucose Deprivation Induced Damage in Rat Brain Slices

Ischemic stroke can cause striatal dopamine efflux that contributes to cell death. Since Kv7 potassium channels regulate dopamine release, we investigated the effects of their pharmacological modulation on dopamine efflux, measured by fast cyclic voltammetry (FCV), and neurotoxicity, in Wistar rat caudate brain slices undergoing oxygen and glucose deprivation (OGD). The Kv7 activators retigabine and ICA27243 delayed the onset, and decreased the peak level of dopamine efflux induced by OGD; and also decreased OGD-induced damage measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Retigabine also reduced OGD-induced necrotic cell death evaluated by lactate dehydrogenase activity assay. The Kv7 blocker linopirdine increased OGD-evoked dopamine efflux and OGD-induced damage, and attenuated the effects of retigabine. Quantitative-PCR experiments showed that OGD caused an ~ 6-fold decrease in Kv7.2 transcript, while levels of mRNAs encoding for other Kv7 subunits were unaffected; western blot experiments showed a parallel reduction in Kv7.2 protein levels. Retigabine also decreased the peak level of dopamine efflux induced by L-glutamate, and attenuated the loss of TTC staining induced by the excitotoxin. These results suggest a role for Kv7.2 in modulating ischemia-evoked caudate damage.

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Neuroprotective effects of adenosine deaminase in the striatum

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15625077 ◽

2016 ◽

Vol 36 (4) ◽

pp. 709-720 ◽

Cited By ~ 7

Author(s):

Risa Tamura ◽

Hiroyuki Ohta ◽

Yasushi Satoh ◽

Shigeaki Nonoyama ◽

Yasuhiro Nishida ◽

...

Keyword(s):

Cerebral Ischemia ◽

Adenosine Deaminase ◽

Neuronal Damage ◽

Brain Slices ◽

Field Potential ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Protective Effects ◽

Neuroprotective Effects ◽

Negative Effect

Adenosine deaminase (ADA) is a ubiquitous enzyme that catabolizes adenosine and deoxyadenosine. During cerebral ischemia, extracellular adenosine levels increase acutely and adenosine deaminase catabolizes the increased levels of adenosine. Since adenosine is a known neuroprotective agent, adenosine deaminase was thought to have a negative effect during ischemia. In this study, however, we demonstrate that adenosine deaminase has substantial neuroprotective effects in the striatum, which is especially vulnerable during cerebral ischemia. We used temporary oxygen/glucose deprivation (OGD) to simulate ischemia in rat corticostriatal brain slices. We used field potentials as the primary measure of neuronal damage. For stable and efficient electrophysiological assessment, we used transgenic rats expressing channelrhodopsin-2, which depolarizes neurons in response to blue light. Time courses of electrically evoked striatal field potential (eFP) and optogenetically evoked striatal field potential (optFP) were recorded during and after oxygen/glucose deprivation. The levels of both eFP and optFP decreased after 10 min of oxygen/glucose deprivation. Bath-application of 10 µg/ml adenosine deaminase during oxygen/glucose deprivation significantly attenuated the oxygen/glucose deprivation-induced reduction in levels of eFP and optFP. The number of injured cells decreased significantly, and western blot analysis indicated a significant decrease of autophagic signaling in the adenosine deaminase-treated oxygen/glucose deprivation slices. These results indicate that adenosine deaminase has protective effects in the striatum.

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Effect of Barbiturates on Hydroxyl Radicals, Lipid Peroxidation, and Hypoxic Cell Death in Human NT2-N Neurons

Anesthesiology ◽

10.1097/00000542-200003000-00020 ◽

2000 ◽

Vol 92 (3) ◽

pp. 764-774 ◽

Cited By ~ 55

Author(s):

Runar Almaas ◽

Ola D. Saugstad ◽

David Pleasure ◽

Terje Rootwelt

Keyword(s):

Lipid Peroxidation ◽

Cell Death ◽

Hydroxyl Radicals ◽

Glucose Deprivation ◽

Hypoxic Cell ◽

Antioxidant Action ◽

Dihydroxybenzoic Acid ◽

Neuroprotective Effects ◽

Oxygen And Glucose Deprivation ◽

Lactate Dehydrogenase Release

Background Barbiturates have been shown to be neuroprotective in several animal models, but the underlying mechanisms are unknown. In this study, the authors investigated the effect of barbiturates on free radical scavenging and attempted to correlate this with their neuroprotective effects in a model of hypoxic cell death in human NT2-N neurons. Methods Hydroxyl radicals were generated by ascorbic acid and iron and were measured by conversion of salicylate to 2,3-dihydroxybenzoic acid. The effect of barbiturates on lipid peroxidation measured as malondialdehyde and 4-hydroxynon-2-enal was also investigated. Hypoxia studies were then performed on human NT2-N neurons. The cells were exposed to 10 h of hypoxia or combined oxygen and glucose deprivation for 3 or 5 h in the presence of thiopental (50-600 microM), methohexital (50-400 microM), phenobarbital (10-400 microM), or pentobarbital (10-400 microM), and cell death was evaluated after 24 h by lactate dehydrogenase release. Results Pentobarbital, phenobarbital, methohexital, and thiopental dose-dependently inhibited formation of 2,3-dihydroxybenzoic acid and iron-stimulated lipid peroxidation. There were significant but moderate differences in antioxidant action between the barbiturates. While phenobarbital (10-400 microM) and pentobarbital (10-50 microM) increased lactate dehydrogenase release after combined oxygen and glucose deprivation, thiopental and methohexital protected the neurons at all tested concentrations. At a higher concentration (400 microM), pentobarbital also significantly protected the neurons. At both 50 and 400 microM, thiopental and methohexital protected the NT2-N neurons significantly better than phenobarbital and pentobarbital. Conclusions Barbiturates differ markedly in their neuroprotective effects against combined oxygen and glucose deprivation in human NT2-N neurons. The variation in neuroprotective effects could only partly be explained by differences in antioxidant action.

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Oxygen and Glucose Deprivation in an Organotypic Hippocampal Slice Model of the Developing Rat Brain: The Effects on N-Methyl-d-Aspartate Subunit Composition

Anesthesia & Analgesia ◽

10.1213/ane.0b013e3181a27e37 ◽

2009 ◽

Vol 109 (1) ◽

pp. 205-210 ◽

Cited By ~ 10

Author(s):

Lisa Wise-Faberowski ◽

Prairie Neeley Robinson ◽

Sarah Rich ◽

David S. Warner

Keyword(s):

Rat Brain ◽

Hippocampal Slice ◽

Glucose Deprivation ◽

Subunit Composition ◽

Oxygen And Glucose Deprivation ◽

Developing Rat

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Effects of S-adenosyl-l-methionine on lipid peroxidation and glutathione levels in rat brain slices exposed to reoxygenation after oxygen-glucose deprivation

Neuroscience Letters ◽

10.1016/s0304-3940(01)02475-2 ◽

2002 ◽

Vol 318 (2) ◽

pp. 103-107 ◽

Cited By ~ 12

Author(s):

J.P De La Cruz ◽

M.A Villalobos ◽

M.A Cuerda ◽

A Guerrero ◽

J.A González-Correa ◽

...

Keyword(s):

Lipid Peroxidation ◽

Rat Brain ◽

Brain Slices ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation

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Early modifications in N-methyl-d-aspartate receptor subunit mRNA levels in an oxygen and glucose deprivation model using rat hippocampal brain slices

Neuroscience ◽

10.1016/j.neuroscience.2009.09.019 ◽

2009 ◽

Vol 164 (3) ◽

pp. 1119-1126 ◽

Cited By ~ 15

Author(s):

S. Dos-Anjos ◽

B. Martínez-Villayandre ◽

S. Montori ◽

C.C. Pérez-García ◽

A. Fernández-López

Keyword(s):

Brain Slices ◽

Glucose Deprivation ◽

Mrna Levels ◽

Receptor Subunit ◽

Oxygen And Glucose Deprivation ◽

Subunit Mrna ◽

Aspartate Receptor ◽

Deprivation Model

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Contribution of ginsenosides Rg1, Rb1 to the neuroprotective effect of Panax notoginseng in mouse organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation

Vietnam Journal of Science Technology and Engineering ◽

10.31276/vjste.63(2).64-69 ◽

2021 ◽

Vol 63 (2) ◽

pp. 64-69

Author(s):

Nguyen Thi Thanh Loan ◽

◽

Le Thi Xoan ◽

Pham Thi Nguyet Hang ◽

Nguyen Van Tai ◽

...

Keyword(s):

Hippocampal Slice ◽

Cell Damage ◽

Neuroprotective Effect ◽

Neuronal Cell ◽

Glucose Deprivation ◽

Panax Notoginseng ◽

Ginsenoside Rg1 ◽

Neuroprotective Effects ◽

Oxygen And Glucose Deprivation ◽

Mk 801

We previously demonstrated that Panax notoginseng (pNG) root extract treatments exertedneuroprotective effects on brain injuries using middle cerebral artery occlusion in mice. The present study aims to investigate the neuroprotective effects of PNG extract and its ginsenosides Rg1 and Rb1 on ischemic neuronal damage caused by oxygen and glucose deprivation (OGD) in mouse organotypic hippocampal slice cultures (OHSCs). Before the experiments, hippocampal slices collected from 7-day-old Swiss mice were cultured for 7 days. OGD was triggered in OHSCs for 30, 60, or 90 min with the aim of finding the optimal period of OGD for drug testing. PNG extract (10, 30 μg/ml), ginsenosides Rg1 and Rb1 (5, 25 μM), or MK-801 25 μM, a reference drug, was added to the culture medium 24 h before OGD and these treatments were continued for 24 h after the optimum 60-min period of OGD. After 24 h of OGD exposure, the measurement of propidium iodide uptake was analysed in OHSCs to evaluate neuronal cell damage. The results showed that OGD time-dependently increased PI uptake of the OHSCs. PNG 30 μg/ml treatment reduced the OGD-induced neuronal cell damage in OHSCs. Ginsenosides Rg1 25 μM, Rb1 (5, 25 μM), as well as MK-801 (25 μM) significantly inhibited PI uptake 24 h after OGD exposure. However, ginsenoside Rg1 5 μM did not show any significant effects on the OGD-induced neuronal cell damage. These findings indicated that ginsenosides Rg1 and Rb1 contributed to the neuroprotective effects of PNG against ischemic damage in OHSCs and the neuroprotective effect of ginsenoside Rb1 was stronger than that of ginsenoside Rg1.

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