Do inhaled anesthetics contribute to postoperative cognitive dysfunction? This important topic is difficult to study clinically because of the confounding effects of surgery. Animal models are being increasingly used to try to determine the specific effects of anesthesia.
Dr. Feng Tau, Department of Anesthesia and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues examined the effects of isoflurane exposure on learning and memory and tau protein phosphorylation in a mouse model of Alzheimer’s disease. Their results are discussed in the article “The Role of Hippocampal Tau Protein Phosphorylation in Isoflurane-Induced Cognitive Dysfunction in Transgenic APP695 Mice,” which was published in this month’s issue of Anesthesia and Analgesia. Tau protein, which is associated with microtubules, can destabilize the microtubule when phosphorylated, resulting in neuronal damage and degeneration. Recent work indicates that anesthetics, both volatile and intravenous, can induce tau phosphorylation. Transgenic APP695 mice over-express and deposit the protein beta amyloid, which is a key step in the development of Alzheimer’s disease.
The investigators used the Morris Water Maze test to examine learning and behavior and found that transgenic mice had significantly impaired function compared with the wild type mice 2, 3, and 4 days after 4 hours of 1.0 MAC isoflurane anesthesia. Hippocampal tau protein phosphorylation levels, determined by Western blot analysis, were increased significantly in the transgenic mice compared with the wild type mice before isoflurane, and this difference was enhanced after isoflurane exposure. Total hippocampal tau values in both groups of mice were not changed by isoflurane.
This interesting study combines measures of functional recovery from anesthesia with changes in a key biochemical step in the development of neuronal damage. The transgenic model, with enhanced beta-amyloid deposition, suggests that the effects of volatile anesthetics may be exacerbated in the elderly brain that has already undergone neurodegenerative changes. Translation of animal work to clinical anesthesia remains a huge challenge, but this study is another valuable piece in that veritable jigsaw puzzle.