The effects of propofol on NMDA- or nitric oxide-mediated neurotoxicity in vitro

Shibuta, Satoshi; Varathan, Sriranganathan; Inoue, T; Shimizu, Tomoaki; Tomi, Katsuji; Mashimo, Takashi

doi:10.1097/00001756-200102120-00023

Cited by 20 publications

(18 citation statements)

References 22 publications

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“…Primary cortical cultures were prepared as described previously (Shibuta et al, 1998, 2000, 2001). Rat fetuses at embryonic day 16 were removed surgically from anesthetized pregnant Wistar rats (obtained from Nihon SLC Hamamatus Japan), and their brains were isolated under the microscope.…”

Section: Methodsmentioning

confidence: 99%

“…We used Shibuta's model (Shibuta et al, 1998, 2000, 2001) to evaluate cytotoxicity. Three or four photomicrographs were made of each well shortly before exposing the cells to hypoxia and at the end of the experiment according to the grid arrangement of the dish.…”

Section: Methodsmentioning

confidence: 99%

“…Because neuronal cell death varies precisely with different temperatures and with the ischemic time course, accurate assessment of viable neurons is mandatory. We exposed the cultured neurons to simulate ischemia in a special anoxic incubator (water jacket type, Astec APMW‐36; Astec Japan) and evaluated the neuroprotective effects elicited by hypothermia with our effective culture model (Shibuta et al, 1998, 2000, 2001).…”

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confidence: 99%

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Neuroprotective effect of hypothermia at defined intraischemic time courses in cortical cultures

Varathan

Shibuta

Shimizu

et al. 2001

J of Neuroscience Research

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Many experimental and clinical studies have shown that hypothermia confers cerebroprotective benefits against ischemic insults. Because of the many conflicting reports on hypothermic neuroprotection, we undertook this cellular study to identify the optimal temperature or a range of temperatures for maximal neuroprotection at different times (6-24 hr) during ischemic insults. Cultured Wistar rat cortical neurons were exposed to oxygen deprivation at defined times and temperatures (37 degrees C normothermia, 32 degrees C mild hypothermia, 27 degrees C moderate hypothermia, 22 degrees C deep hypothermia, and 17 degrees C profound hypothermia). The survival rate of neurons was evaluated by assessing viable neurons on photomicrographs. The normothermic group demonstrated a significantly lower survival rate of cultured neurons (6 hr, 80.3% +/- 2.7%; 12 hr, 56.1% +/- 2.1%; 18 hr, 34.2% +/- 1%; 24 hr, 18.1% +/- 2.2%) compared to hypothermic groups (P < 0.001). The survival rate for the profound hypothermic group was significantly reduced (P < 0.01) compared to other hypothermic groups (at 17 degrees C: 12 hr, 85.9% +/- 2.5%, 18 hr, 74.7% +/- 3.7%, 24 hr, 58.7% +/- 2.7%). Almost equal survival rates were observed among mild, moderate, and deep hypothermic groups following <18 hr exposure to hypoxia, but the deep hypothermic group showed a significantly higher survival rate (84.1% +/- 1.6%; P < 0.001) when subjected to hypoxia for 24 hr. In conclusion, hypothermia offers marked neuroprotection against hypoxia, but attenuation of neuronal cell death was less with profound hypothermia compared to mild, moderate, and deep hypothermia. Deep hypothermia affords maximal protection of neurons compared to mild and moderate hypothermia during long-lasting hypoxia (>18 hr).

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Neuroprotective effect of hypothermia at defined intraischemic time courses in cortical cultures

Varathan

Shibuta

Shimizu

et al. 2001

J of Neuroscience Research

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“…However, the mechanism involved in the neuroprotective effect of ketamine has been poorly determined. Ketamine exhibits anesthetic effects by inhibiting NMDA receptors in the central nervous system, where they are widely expressed [24,25]. In this study, NMDA receptor expression was also detected in BV2 cells (data not shown).…”

Section: Discussionmentioning

confidence: 54%

Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

Ding

et al. 2019

Fundamemntal Clinical Pharma

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Microglial inflammation leads to the upregulation of proinflammatory cytokine and proinflammatory enzyme expression, resulting in inflammation‐induced neuronal cell apoptosis. Ketamine, an anesthetic mostly used in critical patients, has been reported to possess neuroprotective effects. However, the potential mechanism is still not well understood. In the present study, we investigated how ketamine attenuates lipopolysaccharide (LPS)‐mediated BV2 cell inflammation. LPS upregulated proinflammatory cytokine and proinflammatory enzyme expression, increased NF‐κB phosphorylation and nuclear translocation, and augmented calcium (Ca2+)/calmodulin‐dependent protein kinase II (CaMK II) phosphorylation and Ca2+ levels in BV2 cells. Ketamine could reverse these LPS‐induced effects. Furthermore, AP5, an inhibitor of NMDA receptors, inhibited LPS‐induced inflammatory effects in BV2 cells, which was similar to the effects of ketamine. Moreover, these effects of ketamine against LPS‐mediated inflammation in BV2 cells could be reversed by D‐serine, an activator of NMDA receptors. The present study suggests that ketamine, by inhibiting NMDA receptors, attenuating Ca2+ levels, and inhibiting CaMK II phosphorylation, NF‐κB phosphorylation and nuclear translocation, may ameliorate LPS‐mediated inflammation in BV2 cells.

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“…[1] The Diprifusor ® system, the first commercial TCI device used worldwide, displays effect-site concentration of propofol (Cep) as well as plasma concentration calculated according to the Marsh model, which is one of the most frequently used pharmacokinetic models for propofol. [2] However, the Marsh model does not adjust for age and weight is the only model covariate.…”

Section: Introductionmentioning

confidence: 99%

The influence of initial target effect-site concentrations of propofol on the similarity of effect-sites concentrations at loss and return of consciousness in elderly female patients with the Diprifusor system

Shibuta

Kanemura

Uchida

et al. 2012

J Anaesthesiol Clin Pharmacol

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Background:Whether effect-site concentrations of propofol (Cep) at loss of consciousness and return of consciousness (LOC and ROC, respectively) in elderly women using Diprifusor are similar is unclear. We investigated whether differences in initial target Cep (Ctarget) alter similarities between Cep values at LOC and ROC.Materials and Methods:In this study, female patients (n = 58, age = 72.5 ± 1.1 years) undergoing knee arthroplasty were administered propofol with Diprifusor. Cep at LOC and ROC were estimated for different Ctarget values (3.0–4.5 μg/ml). Pearson's correlation coefficient analysis and simple regression were performed to assess the relationship between Cep at LOC and ROC for each Ctarget. Differences in correlation coefficients of regression lines obtained from each Ctarget group were determined using the t-test.Results:The different Ctarget groups did not show significant differences in total propofol levels and in Cep values at LOC or ROC. However, Cep at ROC was significantly higher than Cep at LOC when Ctarget was 4.0 and 4.5 μg/ml, whereas these Cep values were not significantly different in low Ctarget groups.Strong positive correlations were observed between Cep at LOC and ROC for all Ctarget groups. Regression coefficients for the different Ctarget groups were not significantly different. Compared to low (≤3.5 μg/ml) Ctarget groups, high Ctarget groups showed significantly shorter time until LOC. Induction quality was not significantly different among the groups.Conclusions:In elderly women, Cep values at LOC are strong predictors of Cep at ROC when Ctarget is 3.0–4.5 μg/ml. High Ctarget groups (≥4.0 μg/ml) exhibited shorter induction times with normal cardiovascular stability.

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The effects of propofol on NMDA- or nitric oxide-mediated neurotoxicity in vitro

Cited by 20 publications

References 22 publications

Neuroprotective effect of hypothermia at defined intraischemic time courses in cortical cultures

Neuroprotective effect of hypothermia at defined intraischemic time courses in cortical cultures

Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

The influence of initial target effect-site concentrations of propofol on the similarity of effect-sites concentrations at loss and return of consciousness in elderly female patients with the Diprifusor system

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