The nature and time course of neuronal vacuolation induced by the N-methyl-d-aspartate antagonist MK-801

1994 ◽  
Vol 87 (1) ◽  
pp. 1-7 ◽  
Author(s):  
R. N. Auer ◽  
K. C. Coulter
Keyword(s):  
Time Course ◽  
Mk 801 ◽  
Neuronal Vacuolation

scholarly journals Proteomic analysis for neuronal vacuolation induced by MK-801 in rat retrosplenial cortex

2011 ◽  
Vol 36 (1) ◽  
pp. 131-133 ◽  
Author(s):  
Motohiro Shiotani ◽  
Kyoko Nakano ◽  
Emiko Yamauchi ◽  
Yoshiya Oda ◽  
Satoru Hosokawa ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Retrosplenial Cortex ◽  
Mk 801 ◽  
Neuronal Vacuolation

NREM delta stimulation following MK-801 is a response of sleep systems

1996 ◽  
Vol 76 (6) ◽  
pp. 3714-3720 ◽  
Author(s):  
I. G. Campbell ◽  
I. Feinberg
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Time Course ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Mk 801 ◽  
Regulatory Systems ◽  
Sleep Centers ◽  
Electroencephalogram Eeg

1. We have previously shown that noncompetitive blockade of the N-methyl-D-aspartate (NMDA)-gated cation channel with ketamine or Dizocilpine maleate (MK-801) increases the intensity of non-rapid-eye-movement (NREM) delta during subsequent sleep. This delta increase [measured as integrated amplitude (IA) in 1- to 4-Hz electroencephalogram (EEG)] occurs in the 12-h period following intraperitoneal injection. However, the 12 h after drug injection is also the period in which these drugs induce neurotoxic changes, raising the possibility that the increased delta represents toxic EEG slowing rather than an increase in the physiological delta waves of NREM sleep. 2. We hypothesized that the time course of delta stimulation could be separated from the time course of neurotoxicity. We tested this hypothesis by injecting 0.3 mg/kg MK-801 at the start of the dark period (DP) and depriving rats of sleep until the onset of the light period (LP) 12 h later. 3. There were two control groups: one received MK-801 at the start of the DP with no further manipulation, and the second received a saline injection at DP onset followed by 12 h of sleep deprivation. The dependent variable was the amount of delta IA in the LP, whose onset was 12 h after MK-801 injection. Total IA in the LP was significantly greater in rats that received MK-801 followed by sleep deprivation than in rats that received sleep deprivation alone or MK-801 alone. 4. This finding indicates that delta stimulation by MK-801 is maintained over 12 h of waking, indicating that the delta increase is not due to toxic EEG slowing or persisting MK-801. Instead, NMDA channel blockade by MK-801 increases the homeostatic need for delta or else directly alters sleep regulatory systems. We speculate that these effects are mediated by hypothalamic sleep centers through control of neuroendocrine pulses that produce both NREM and rapid-eye-movement sleep. 5. Imposing a period of waking between drug administration and sleep onset may prove a generally useful strategy for determining whether a drug affects the homeostatic need for sleep or acutely stimulates sleep systems. This strategy can also help distinguish between toxic and physiological increases in delta EEG.

MK-801 does not prevent impaired cerebrovascular reactivity to CO2 during hypoglycemia in piglets

1993 ◽  
Vol 264 (6) ◽  
pp. H2124-H2130
Author(s):  
P. J. St Jacques ◽  
J. R. Kirsch ◽  
M. N. Diringer ◽  
R. J. Traystman
Keyword(s):  
Nmda Receptor ◽  
Time Course ◽  
Nmda Receptor Antagonist ◽  
Cerebrovascular Reactivity ◽  
Co2 Reactivity ◽  
Resistance Change ◽  
Mk 801 ◽  
Cerebrovascular Resistance ◽  
Cerebrovascular Co2 Reactivity ◽  
Made In

We tested the hypothesis that severe insulin-induced hypoglycemia would depress cerebrovascular reactivity to CO2 via a mechanism that could be prevented by administration of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in infant piglets. Cerebral blood flow (CBF) was measured (microspheres) in 2- to 3-wk-old pentobarbital-anesthetized piglets during hypocapnia, normocapnia, and hypercapnia. Repeat CBF measurements were made either 1 (n = 5) or 2 h (n = 6) after insulin (200 U/kg iv) to elicit the time course of altered reactivity to CO2. Repeat CBF measurements were made in a third group (n = 5) 2 h after treatment with insulin and MK-801 (1.5 mg/kg iv bolus, 0.15 mg.kg-1.h-1 iv infusion) to determine whether any alteration in reactivity to CO2 was due to a mechanism involving the NMDA receptor. Cerebrovascular resistance and cerebral O2 consumption (CMRO2) were calculated with each measurement of CBF. Cerebrovascular response to CO2 (change in cerebrovascular resistance/change in arterial CO2 tension) was ablated in the group of piglets exposed to 1 or 2 h of hypoglycemia (preinsulin 1-h group, 0.038 +/- 0.007; preinsulin 2-h group, 0.023 +/- 0.004 mmHg.ml-1.min.100 g.mmHg CO2(-1)). Treatment with MK-801 did not alter normoglycemic CO2 reactivity (preinsulin, 0.032 +/- 0.005 mmHg.ml-1.min.100 g.mmHg CO2(-1)) and did not prevent ablation of cerebrovascular CO2 reactivity during hypoglycemia. CMRO2 was not affected by hypoglycemia in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals MRI Heralds Secondary Nigral Lesion after Brain Ischemia in Mice: A Secondary Time Window for Neuroprotection

2015 ◽  
Vol 35 (12) ◽  
pp. 1903-1909 ◽  
Author(s):  
Vincent Prinz ◽  
Anna-Maria Hetzer ◽  
Susanne Müller ◽  
Mustafa Balkaya ◽  
Christoph Leithner ◽  
...  
Keyword(s):  
Time Course ◽  
Time Window ◽  
Neuronal Degeneration ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Ischemic Lesion ◽  
Mk 801 ◽  
Delayed Treatment ◽  
Secondary Time

Cerebral ischemia in the territory of the middle cerebral artery (MCA) can induce delayed neuronal cell death in the ipsilateral substantia nigra (SN) remote from the primary ischemic lesion. This exofocal postischemic neuronal degeneration (EPND) may worsen stroke outcomes. However, the mechanisms leading to EPND are poorly understood. Here, we studied the time course of EPND via sequential magnetic resonance imaging (MRI) and immunohistochemistry for up to 28 days after 30 minutes occlusion of the MCA (MCAo) and reperfusion in the mouse. Furthermore, the effects of delayed treatment with FK506 and MK-801 on the development of EPND were investigated. Secondary neuronal degeneration in the SN occurred within the first week after MCAo and was characterized by a marked neuronal cell loss on histology. Sequential neuroimaging examinations revealed transient MRI changes, which were detectable as early as day 4 after MCAo and thus heralding histologic evidence of EPND. Treatment with MK-801, an established anti-excitotoxic agent, conferred protection against EPND even when initiated days after the initial ischemic event, which was not evident with FK506. Our findings define a secondary time window for delayed neuroprotection after stroke, which may provide a promising target for the development of novel therapies.

Anticonflict effect of MK-801 in rats: Time course and chronic treatment studies

1995 ◽  
Vol 51 (4) ◽  
pp. 635-640 ◽  
Author(s):  
Zhongcong C. Xie ◽  
Erica Buckner ◽  
Randall L. Commissaris
Keyword(s):  
Time Course ◽  
Chronic Treatment ◽  
Mk 801 ◽  
Anticonflict Effect

Probability of Transmitter Release at Neocortical Synapses at Different Temperatures

2004 ◽  
Vol 92 (1) ◽  
pp. 212-220 ◽  
Author(s):  
Maxim Volgushev ◽  
Igor Kudryashov ◽  
Marina Chistiakova ◽  
Mikhail Mukovski ◽  
Johannes Niesmann ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Nmda Receptor ◽  
Transmitter Release ◽  
Room Temperature ◽  
Time Course ◽  
Dynamic Properties ◽  
Variable Temperature ◽  
Pyramidal Cells ◽  
Mk 801 ◽  
Release Probability

The probability of transmitter release at synaptic terminals is one of the key characteristics of communication between nerve cells because it determines both the strength and dynamic properties of synaptic connections. To assess the distribution of the release probabilities at excitatory synapses on supragranular pyramidal cells in rat visual cortex, we have used the MK-801, a blocker of the open N-methyl-d-aspartate (NMDA) receptor-gated channels. With this method, the release probability can be calculated from the time course of the blockade of NMDA-receptor mediated postsynaptic currents in the presence of MK-801. At temperatures >32°C, the distribution of release probabilities covered the range from 0.05 to 0.43 [mean: 0.171 ± 0.012 (SE), n = 65], being skewed toward low values. When estimated at room temperature (22–25°C), the release probabilities were significantly lower (mean: 0.123 ± 0.009, n = 54), and almost the whole distribution was restricted to values <0.2. Furthermore, warming from room temperature to >32°C led to a pronounced overshooting increase of the release probability. Taken together, the results of the present study show that release probabilities at synapses formed onto layer 2/3 pyramidal cells in the visual cortex vary significantly, but values >0.3 are rare and the results obtained either at room or variable temperature differ significantly from those made under conditions of constant temperature in the physiological range.

Time course effects of MK-801: The relationship between brain neurochemistry and behavior

1995 ◽  
Vol 36 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Huiliang Dai ◽  
Kerstin Gebhardt ◽  
Robert J. Carey
Keyword(s):  
Time Course ◽  
Mk 801 ◽  
And Behavior ◽  
The Relationship

scholarly journals Improved Therapeutic Window for Treatment of Histotoxic Hypoxia with a Free Radical Spin Trap

1995 ◽  
Vol 15 (6) ◽  
pp. 948-952 ◽  
Author(s):  
Jörg B. Schulz ◽  
Russell T. Matthews ◽  
Bruce G. Jenkins ◽  
Preetinder Brar ◽  
M. Flint Beal
Keyword(s):  
Free Radical ◽  
Time Course ◽  
Spin Trap ◽  
Glutamate Release ◽  
Lactate Production ◽  
Nmda Antagonist ◽  
Therapeutic Window ◽  
Nmda Antagonists ◽  
Mk 801 ◽  
Histotoxic Hypoxia

The therapeutic time window for N-methyl-d-aspartate (NMDA) antagonists, non-NMDA antagonists, and glutamate release inhibitors in focal models of ischemia appears to be about 1–2 h. In contrast, a free radical spin trap was found to have an improved therapeutic window. We compared the therapeutic time windows of the NMDA antagonist dizolcilpine maleate (MK-801), the glutamate release inhibitor lamotrigine, and the free radical spin trap n-tert-butyl-α-(2-sulfophenyl)-nitrone (S-PBN) against striatal lesions produced by the mitochondrial toxin malonate, which produces histotoxic hypoxia. Lamotrigine exerted neuroprotective effects when administered at 1 h before malonate injections. MK-801 protected at 1 h before and 1 h after malonate injections, whereas S-PBN showed efficacy when administered up to 6 h after malonate injections. Striatal injections of malonate produced a rapid increase in lactate production and early changes in diffusion-weighted imaging as assessed by magnetic resonance imaging. Therefore, the time course to evolve a lesion in our model of histotoxic hypoxia is comparable with that of other models of focal ischemia. These findings provide direct evidence that a free radical spin trap has an improved therapeutic window compared to an NMDA antagonist and a glutamate release inhibitor. This could be a therapeutic advantage in the treatment of clinical stroke patients.

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