• Yuanlin Dong, Guohua Zhang, Bin Zhang, Robert D Moir, Weiming Xia, Edward R Marcantonio, Deborah J Culley, Gregory Crosby, Rudolph E Tanzi, and Zhongcong Xie.
• Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
• Arch. Neurol. 2009 May 1;66(5):620-31.

ObjectiveTo assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on apoptosis and beta-amyloid protein (Abeta) levels in vitro and in vivo. Subjects Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein.InterventionsHuman H4 neuroglioma cells stably transfected to express full-length amyloid precursor protein were exposed to 4.1% sevoflurane for 6 hours. Mice received 2.5% sevoflurane for 2 hours. Caspase-3 activation, apoptosis, and Abeta levels were assessed.ResultsSevoflurane induced apoptosis and elevated levels of beta-site amyloid precursor protein-cleaving enzyme and Abeta in vitro and in vivo. The caspase inhibitor Z-VAD decreased the effects of sevoflurane on apoptosis and Abeta. Sevoflurane-induced caspase-3 activation was attenuated by the gamma-secretase inhibitor L-685,458 and was potentiated by Abeta. These results suggest that sevoflurane induces caspase activation which, in turn, enhances beta-site amyloid precursor protein-cleaving enzyme and Abeta levels. Increased Abeta levels then induce further rounds of apoptosis.ConclusionsThese results suggest that inhalational anesthetic sevoflurane may promote Alzheimer disease neuropathogenesis. If confirmed in human subjects, it may be prudent to caution against the use of sevoflurane as an anesthetic, especially in those suspected of possessing excessive levels of cerebral Abeta.

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