Article

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

Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Annals of Neurology (Impact Factor: 9.98). 12/2008; 64(6):618-27. DOI: 10.1002/ana.21548
Source: PubMed

ABSTRACT

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 (Abeta) in cultured cells. However, the in vivo relevance has not been addressed.
We therefore set out to determine effects of isoflurane on caspase activation and levels of beta-site amyloid precursor protein-cleaving enzyme (BACE) and Abeta in naive mice, using Western blot, immunohistochemistry, and reverse transcriptase polymerase chain reaction.
Here we show for 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 BACE 6 hours after anesthesia in mouse brain. Isoflurane anesthesia induces caspase activation, and increases levels of BACE and Abeta up to 24 hours after anesthesia. Isoflurane may increase BACE levels by reducing BACE degradation. Moreover, the Abeta aggregation inhibitor, clioquinol, was able to attenuate isoflurane-induced caspase-3 activation in vivo.
Given that transient insults to brain may lead to long-term brain damage, these findings suggest that isoflurane may promote Alzheimer's disease neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending human study confirmation.

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Available from: Robert D Moir, Sep 16, 2014
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    • "Firstly, NIRS oximeters were put on forehead and reflected the condition of superficial cerebral cortex, so it might miss embolism, hypoperfusion and desaturation far from superficial cortex [46] . Secondly, Neurotoxicity such as neuroinflammation and Aβ generation also contribute to POCD474849, which affect the predictive performance of ScO 2 . Thirdly, even if absolute value of 50 and 80 % of baseline were regarded as safe limits for ScO 2 to prevent cerebral ischemia, cognitive dysfunction were still observed in the present and previous studies [13]. "
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