The Common Inhalation Anesthetic Isoflurane Induces Caspase Activation and Increases Amyloid β-Protein Level In Vivo

objective: An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer's disease. The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis, and to increase levels and aggregation of Alzheimer's disease-associated amyloid (beta-protein (A beta) in cultured cells. However, the in vivo relevance has not been addressed. Methods: We therefore set out to determine effects of isoflurane on caspase activation and levels of beta-site amyloid precursor protein-cleaving enzyme (BACE) and A beta in naive mice, using Western blot, immunohistochemistry, and reverse transcriptase polymerase chain reaction. \ Results: Here we show or the first time that a clinically relevant isoflurane anesthesia (1.4% isoflurane for 2 hours) leads to caspase activation and modest increases in levels of BALE 6 hours after anesthesia in mouse brain. Isoflurane anesthesia induces caspase activation, and increases levels of BACE and A beta tip to 24 hours after anesthesia. Isoflurane may increase BACE levels by reducing BACE degradation. Moreover, the A beta aggregation inhibitor, clioquinol, was able to attenuate isoflurane-induced caspase-3 activation in vivo. Interpretation: Given that transient insults to brain may lead to long-term brain damage, these findings suggest that isoflurane tray promote Alzheimer's disease neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending human study confirmation.