Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation
Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hyp...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2009-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2009/705379 |
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| author | Yi Chang Jie-Jen Lee Cheng-Ying Hsieh George Hsiao Duen-Suey Chou Joen-Rong Sheu |
| author_facet | Yi Chang Jie-Jen Lee Cheng-Ying Hsieh George Hsiao Duen-Suey Chou Joen-Rong Sheu |
| author_sort | Yi Chang |
| collection | DOAJ |
| description | Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor-α
(TNF-α) and interleukin-1β (IL-1β). 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 250 μM) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1β release in primary cultured microglia. However, ketamine (100 and 250 μM) did not significantly inhibit the LPS-induced TNF-α production in microglia, except at the higher concentration (500 μM). 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. |
| format | Article |
| id | doaj-art-65ca6b06db4a44f78d6d2f5c7f39e2a5 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-65ca6b06db4a44f78d6d2f5c7f39e2a52025-08-20T02:23:48ZengWileyMediators of Inflammation0962-93511466-18612009-01-01200910.1155/2009/705379705379Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial ActivationYi Chang0Jie-Jen Lee1Cheng-Ying Hsieh2George Hsiao3Duen-Suey Chou4Joen-Rong Sheu5Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, School of Medicine, Fu-Jen Catholic University, 24205 Taipei, TaiwanDepartment of Surgery, Mackay Memorial Hospital, Taipei 10449, TaiwanDepartment of Pharmacology, Taipei Medical University, 11031 Taipei, TaiwanDepartment of Pharmacology, Taipei Medical University, 11031 Taipei, TaiwanDepartment of Pharmacology, Taipei Medical University, 11031 Taipei, TaiwanDepartment of Pharmacology, Taipei Medical University, 11031 Taipei, TaiwanMicroglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). 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 250 μM) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1β release in primary cultured microglia. However, ketamine (100 and 250 μM) did not significantly inhibit the LPS-induced TNF-α production in microglia, except at the higher concentration (500 μM). 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.http://dx.doi.org/10.1155/2009/705379 |
| spellingShingle | Yi Chang Jie-Jen Lee Cheng-Ying Hsieh George Hsiao Duen-Suey Chou Joen-Rong Sheu Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation Mediators of Inflammation |
| title | Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation |
| title_full | Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation |
| title_fullStr | Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation |
| title_full_unstemmed | Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation |
| title_short | Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation |
| title_sort | inhibitory effects of ketamine on lipopolysaccharide induced microglial activation |
| url | http://dx.doi.org/10.1155/2009/705379 |
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