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Anesthesiology
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of the present study was to investigate effects, in normothermic conditions, of acute or repeated exposure to sevoflurane, a halogenated anesthetic agent, on hippocampal tau phosphorylation and spatial memory in adult mice. Methods 5 to 6-month-old C57Bl6/J mice were submitted to acute (1 h) or repeated (five exposures of 1h every month) anesthesia using 1.5 or 2.5% sevoflurane, in normothermic conditions. In the acute protocol, animals were sacrificed 1 and 24 h after exposure. In the chronic protocol, spatial memory was evaluated using the Morris water maze following the fourth exposure, and tau phosphorylation evaluated 1 month following the last exposure using bi- and mono-dimensional electrophoresis. Results Acute sevoflurane anesthesia in normothermic conditions led to a significant dose-dependent and reversible hippocampal tau phosphorylation, 1 h following the end of exposure (P < 0.001). Conversely, repeated anesthesia led to persistent tau hyperphosphorylation and significant memory impairments, as seen in the retention phase of the Morris water maze in sevoflurane-anesthesized animals. These pathologic features may be related to the activation of both Akt and Erk pathways. Conclusions The present study demonstrates, in mice, that sevoflurane exposure is associated with increased tau phosphorylation through specific kinases activation and spatial memory deficits. These data support a correlation between exposures to this anesthetic agent and cognitive decline....
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