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...
| Autores principales: | , , , , , |
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| Formato: | Artículo |
| Lenguaje: | English |
| Publicado: |
Hindawi Limited
2009-01-01
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| Colección: | Mediators of Inflammation |
| Acceso en línea: | http://dx.doi.org/10.1155/2009/705379 |
| Sumario: | 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. |
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| ISSN: | 0962-9351 1466-1861 |