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RESEARCH PRODUCT

Additional file 3 of Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”

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Additional file 3: Figure S3. Mechanisms of neuroprotection by ketamine. Ketamine is a “glutamate modulator.” It exerts its effect basically at two levels: a) presynaptic, inhibiting the release of glutamate and b) post-synaptic, acting as a competitive blocker of N-Methyl-D-Aspartate receptors, thereby excitotoxic injury through inhibiting the entry of calcium into cells, the formation of nitric oxide and oxygen free radicals. Modulates glucose metabolism and the generation of mitochondrial ATP. Inhibits the apoptotic phenomenon. Additionally, it inhibits spreading depolarizations and acts as an antithrombotic and anti-inflammatory by inhibiting platelet aggregation and the production and release of cytokines by the microglia. IL-8: interleukin-8; TNF: tumor necrosis factor; Ca++: calcium; K+: potassium; OFR: oxygen free radicals; ATP: adenosine triphosphate; CBF: cerebral blood flow.