Nicholas P Franks

....

....

..Recent work suggests that the thalamus and the neuronal networks that regulate its activity are the key to understanding how anaesthetics cause loss of consciousness...

..In this review, we examine the evidence that anesthetic-induced loss of consciousness may be caused by actions on the neuronal pathways that produce natural sleep...

..Xenon inhibits NMDA receptors by competing with glycine at the glycine-binding site. We test the hypothesis that inhibition of the NMDA receptor at the glycine site underlies xenon neuroprotection against hypoxia-ischemia...

..If applied to humans, these data suggest that low (subanesthetic) concentrations of xenon in combination with mild hypothermia may provide a safe and effective therapy for perinatal asphyxia...

..GABA(B) receptors on histaminergic neurons were dispensable for all behaviors examined. Synaptic inhibition of histaminergic cells by GABA(A) receptors, however, was essential for habituation to a novel environment...

..These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury...

..Therefore, the current study sought to investigate xenon's putative protective properties against anesthetic-induced neuronal apoptosis...

..Overall, our results support the idea that GABAergic anesthetics such as propofol exert their effects, at least in part, by modulating hypothalamic sleep pathways...

..However, the site of action of these agents on the NMDA receptor is unknown. The authors show that xenon and isoflurane compete for the binding of the coagonist glycine on the NMDA receptor NR1 subunit...

..These results imply a previously unexpected role for TASK-3 channels in the cellular mechanisms underlying these behaviors and suggest that endogenous modulators of these channels may regulate theta oscillations...

..We summarize recent in vitro and in vivo studies on the actions of helium and the other inert gases, and discuss their potential to be used as neuroprotective agents...

..The acyl azide etomidate may prove to be a useful new photolabel to identify anesthetic binding sites on the GABA(A) receptor or other putative targets...

..We further show that the protocol used by previous workers to prepare hypoxic solutions of arachidonic acid results in the removal of the compound from solution...

..Our data suggest that the neuroprotective effect of dexmedetomidine is mediated by activation of the alpha2A adrenergic receptor subtype...

..These observations provide a novel explanation for how copper and zinc might affect neuronal excitability under both normal physiological conditions, as well as during diseases in which copper or zinc homeostasis has been disrupted...

..Finally, we show that Glu306, an amino acid that has previously been found to be important in the modulation of TREK-1 by arachidonic acid, membrane stretch and internal pH, is critical for the activating effects of the anesthetic gases...

..The "inert" gas xenon has been shown to be an effective neuroprotectant in a variety of in vitro and in vivo models of neuronal injury. We examined its neuroprotective properties in an in vitro model of traumatic brain injury...

..The L159A mutation in LyTASK disrupts the stereoselective response to isoflurane while having no effect on the pH sensitivity of the channel, suggesting this critical amino acid may form part of an anesthetic binding site...

..7 +/- 0.8%). CONCLUSIONS: Although xenon does expand small air and oxygen bubbles, the extent to which this occurs under clinically relevant conditions of concentration and temperature is modest...

..These issues will be important when considering drug strategies designed to target extrasynaptic GABA(A) receptors in the treatment of sleep disorders and other neurological conditions...

..The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors...

..Here we identify specific amino acids important for xenon binding to the NMDA receptor, with the aim of finding silent mutations that eliminate xenon binding but leave normal receptor function intact...

..Because these are the conditions that are most relevant to synaptic transmission, the authors conclude that AMPA receptors are unlikely to play a major role in the production of the anesthetic state by inhalational agents...

..Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial...

..The increased release of GABA at the terminals of the VLPO inhibits TMN firing, which is required for the sedative response...

..CONCLUSION: These data indicate that CPB-induced neurologic and neurocognitive dysfunction can be attenuated by the administration of xenon, potentially related to its neuroprotective effect via N-methyl-D-aspartate receptor antagonism...

..0009). CONCLUSIONS: In this model of transient focal cerebral ischemia, xenon administration improved both functional and histologic outcome...

..Studies are proposed to determine whether xenon can be used as a neuroprotectant in certain clinical settings...

..The long-term neurological function data corroborated these morphological data. Our study demonstrates that the combination of xenon and Dex offers neuroprotection additively in vitro and synergistically in vivo...

..These data suggest that the difference in neuropsychological activity between nitrous oxide and xenon is partly due to their differential effects on the mesolimbic dopamine system...

..These structures show anesthetic-protein interactions at the atomic level...