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-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). 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 microM) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1beta release in primary cultured microglia. However, ketamine (100 and 250 microM) did not significantly inhibit the LPS-induced TNF-alpha production in microglia, except at the higher concentration (500 microM). 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.
authors.affiliation: Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, School of Medicine, Fu-Jen Catholic University, 24205 Taipei, Taiwan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Hsieh
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
authors.forename: Duen-Suey
authors.initials: DS
authors.lastname: Chou
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu