Modeling Post-Operative Cognitive Dysfunction in Zebrafish

Abstract

Permanent post-operative cognitive dysfunction (POCD) is a grim outcome to an estimated 6% of elderly surgical patients. Volatile anesthetics impact neuronal tissue independent of effects attributed to the physical trauma of the surgery itself. While it is recognized that all aspects related to surgery may contribute to cognitive loss in some manner, the present paper focuses on the role of volatile anesthetics in promoting POCD. There is an increased risk of onset and progression of Alzheimer’s disease (AD) from POCD, implying that the neuropathogenesis between the two is similar. Human studies, being ethically limited in scope, require animal models as a substitute. While the literature using rodent models contains valuable information, we believe that the accessible and practical zebrafish will greatly enhance our further understanding of the molecular mechanism of POCD as it relates to AD. Disease genes and fundamental neurobehaviors of these teleost fish mirror those of mammals and humans, validating their use as a core research model for AD. Since the gradual senescence seen in zebrafish also resembles that found in humans, we numerically correlated the two lifespans, offering researchers a computational tool. Zebrafish, being aquatic animals, necessitates the use of miscible compounds, such as trifluoroethanol, whose anesthetic potency we are presenting. We also review the rodent and zebrafish literature relevant to POCD. Continued research with the leading-edge zebrafish unlocks the possibility that, in the future, perioperative intervention will prevent POCD.