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Microglial inflammation leads to the upregulation of proinflammatory cytokine and proinflammatory enzyme expression, resulting in inflammation-induced neuronal cell apoptosis. Ketamine, an anesthetic mostly used in critical patients, has been reported to possess neuroprotective effects. However, the potential mechanism is still not well understood. In the present study, we investigated how ketamine attenuates lipopolysaccharide (LPS)-mediated BV2 cell inflammation. LPS upregulated proinflammatory cytokine and proinflammatory enzyme expression, increased NF-κB phosphorylation and nuclear translocation, and augmented calcium (Ca )/calmodulin-dependent protein kinase II (CaMK II) phosphorylation and Ca levels in BV2 cells. Ketamine could reverse these LPS-induced effects. Furthermore, AP5, an inhibitor of NMDA receptors, inhibited LPS-induced inflammatory effects in BV2 cells, which was similar to the effects of ketamine. Moreover, these effects of ketamine against LPS-mediated inflammation in BV2 cells could be reversed by D-serine, an activator of NMDA receptors. The present study suggests that ketamine, by inhibiting NMDA receptors, attenuating Ca levels, and inhibiting CaMK II phosphorylation, NF-κB phosphorylation and nuclear translocation, may ameliorate LPS-mediated inflammation in BV2 cells.
This article was published in the following journal.
Name: Fundamental & clinical pharmacology
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A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.
A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.
A neuronal protein consisting of three PDZ DOMAINS, an SH3 DOMAIN, and a C-terminal guanylate kinase-like region (see MAGUK PROTEINS). It localizes to the POST-SYNAPTIC DENSITY and associates with the cytoplasmic tail of NMDA RECEPTORS and SHAKER POTASSIUM CHANNELS, playing a critical role in NMDA receptor-mediated SYNAPTIC PLASTICITY.
An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).
An Ig domain-containing membrane receptor that is expressed by TH1 CELLS. It regulates the activation of MACROPHAGES and inhibits TH1-mediated auto- and alloimmune responses to promote IMMUNE TOLERANCE.
Cytokine Tumour Necrosis Factor (TNF)
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Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...