54 Citations (Scopus)

Abstract

Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor- x03B1; (TNF- x03B1;) and interleukin-1 x03B2; (IL-1 x03B2;). Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250x02009; x03BC;M) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1 x03B2; release in primary cultured microglia. However, ketamine (100 and 250x02009; x03BC;M) did not significantly inhibit the LPS-induced TNF- x03B1; production in microglia, except at the higher concentration (500x02009; x03BC;M). Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2) phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.

Original languageEnglish
Article number705379
JournalMediators of Inflammation
Volume2009
DOIs
Publication statusPublished - 2009

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Ketamine
Lipopolysaccharides
Microglia
Interleukin-1
Nitric Oxide
Tumor Necrosis Factor-alpha
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Respiratory Insufficiency
Hypotension
Brain Injuries
Anesthetics
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

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title = "Inhibitory effects of ketamine on lipopolysaccharide-induced microglial activation",
abstract = "Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor- x03B1; (TNF- x03B1;) and interleukin-1 x03B2; (IL-1 x03B2;). Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250x02009; x03BC;M) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1 x03B2; release in primary cultured microglia. However, ketamine (100 and 250x02009; x03BC;M) did not significantly inhibit the LPS-induced TNF- x03B1; production in microglia, except at the higher concentration (500x02009; x03BC;M). Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2) phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.",
author = "Sheu, {Joen Rong} and Yi Chang and Lee, {Jie Jen} and Hsieh, {Cheng Ying} and George Hsiao and Chou, {Duen Suey}",
year = "2009",
doi = "10.1155/2009/705379",
language = "English",
volume = "2009",
journal = "Mediators of Inflammation",
issn = "0962-9351",
publisher = "Hindawi Publishing Corporation",

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TY - JOUR

T1 - Inhibitory effects of ketamine on lipopolysaccharide-induced microglial activation

AU - Sheu, Joen Rong

AU - Chang, Yi

AU - Lee, Jie Jen

AU - Hsieh, Cheng Ying

AU - Hsiao, George

AU - Chou, Duen Suey

PY - 2009

Y1 - 2009

N2 - Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor- x03B1; (TNF- x03B1;) and interleukin-1 x03B2; (IL-1 x03B2;). Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250x02009; x03BC;M) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1 x03B2; release in primary cultured microglia. However, ketamine (100 and 250x02009; x03BC;M) did not significantly inhibit the LPS-induced TNF- x03B1; production in microglia, except at the higher concentration (500x02009; x03BC;M). Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2) phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.

AB - Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor- x03B1; (TNF- x03B1;) and interleukin-1 x03B2; (IL-1 x03B2;). Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250x02009; x03BC;M) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1 x03B2; release in primary cultured microglia. However, ketamine (100 and 250x02009; x03BC;M) did not significantly inhibit the LPS-induced TNF- x03B1; production in microglia, except at the higher concentration (500x02009; x03BC;M). Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2) phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.

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