Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation

• Main Authors: Yi Chang (Author), Jie-Jen Lee (Author), Cheng-Ying Hsieh (Author), George Hsiao (Author), Duen-Suey Chou (Author), Joen-Rong Sheu (Author)
• Format: Book
• Published: Hindawi Limited, 2009-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 0962-9351; 1466-1861; 10.1155/2009/705379
• Keywords: Pathology; RB1-214
• Source: Mediators of Inflammation, Vol 2009 (2009)

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.