Protective effect of non-competitive NMDA antagonist MK-801 in methyl mercury induced neuronal injury

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 μm in depth by super-fusion with the membrane-permeant indo-1 acetoxymethyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 μM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18–22 Hz poly spikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.

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INTERACTION BETWEEN THE NONCOMPETITIVE NMDA ANTAGONIST MK-801 AND MORPHINE: EVALUATION BY AMBULATORY ACTIVITY IN MICE.

Clinical Neuropharmacology ◽

10.1097/00002826-199202001-01239 ◽

1992 ◽

Vol 15 ◽

pp. 635B

Author(s):

Y. Iijima ◽

T. Asami ◽

H. Kuribara ◽

I. Ida ◽

T. Higuchi ◽

...

Keyword(s):

Nmda Antagonist ◽

Ambulatory Activity ◽

Mk 801

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Isoflurane and Propofol Block Neurotoxicity Caused by MK-801 in the Rat Posterior Cingulate/Retrosplenial Cortex

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199702000-00006 ◽

1997 ◽

Vol 17 (2) ◽

pp. 168-174 ◽

Cited By ~ 38

Author(s):

Vesna Jevtović-Todorović ◽

Charity O. Kirby ◽

John W. Olney

Keyword(s):

Brain Injury ◽

Neuronal Degeneration ◽

Nmda Antagonist ◽

Retrosplenial Cortex ◽

Acute Brain Injury ◽

Nmda Antagonists ◽

General Anesthetics ◽

General Anesthetic ◽

Mk 801 ◽

Anesthetic Agents

In acute brain injury syndromes, the potent N-methyl-D-aspartate (NMDA) antagonist, MK-801, can prevent neuronal degeneration, and the general anesthetics, isoflurane and propofol, may also provide neuroprotective benefits. An obstacle to the use of NMDA antagonists for neuroprotective purposes is that they can cause a neurotoxic vacuole reaction in cerebrocortical neurons. This study demonstrates the ability of isoflurane and propofol to prevent the neurotoxic vacuole reaction induced by MK-801. Low sedative doses of inhaled isoflurane (1%) or intravenous (i.v.) propofol (7.5 mg/kg/h) were as effective as higher general anesthetic doses. Thus, in the clinical management of acute brain injury conditions such as stroke and brain trauma, administration of one of these anesthetic agents together with an NMDA antagonist may be an excellent formula for obtaining optimal neuroprotection while eliminating serious side effects.

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Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

10.1101/793398 ◽

2019 ◽

Author(s):

Gabriela P. Silote ◽

Sabrina F.S. de Oliveira ◽

Deidiane E. Ribeiro ◽

Mayara S. Machado ◽

Roberto Andreatini ◽

...

Keyword(s):

Nmda Antagonist ◽

Inhibitory Avoidance ◽

Nmda Receptor Antagonist ◽

Mixed Effects ◽

Antidepressant Effect ◽

List Type ◽

Mk 801 ◽

New Findings ◽

Male Wistar Rats ◽

Animal Tests

AbstractKetamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.HighlightsKetamine induces mixed effects in animal anxiety testsFew studies investigated the individual effects of S-ketamine in anxiety/fear testsNone study evaluated the effects of R-Ketamine on anxiety/fear-related behaviorsSystemic ketamine does not affect panic-like behaviors in the elevated T-maze

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Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801

Developmental Brain Research ◽

10.1016/0165-3806(91)90206-x ◽

1991 ◽

Vol 64 (1-2) ◽

pp. 37-41 ◽

Cited By ~ 17

Author(s):

Jan A. Gorter ◽

Monica Veerman ◽

Majid Mirmiran ◽

Nico P.A. Bos ◽

Michael A. Corner

Keyword(s):

Spectral Analysis ◽

Nmda Antagonist ◽

Neonatal Rats ◽

Mk 801

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The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195

NeuroImmunoModulation ◽

10.1159/000519779 ◽

2021 ◽

pp. 1-9

Author(s):

Hui Li ◽

Weijia Du ◽

Yawei Yuan ◽

Jingjing Xue ◽

Qiang Li ◽

...

Keyword(s):

Inflammatory Response ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Escape Latency ◽

Neuronal Cells ◽

Neuronal Injury ◽

Morris Water Maze Test ◽

Picroside Ii ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Introduction: Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. Methods: The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. Results: The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. Conclusion: Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

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