Intergenerational Perioperative Neurocognitive Disorder

Simple Summary Hundreds of millions of patients of all ages undergo general anesthesia for surgery or periods of sedation each year, making the adverse effects of general anesthesia (GA)/surgery a public health concern of paramount importance. The accelerated neurocognitive decline after GA/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem. Advanced age, which tracks with an increasing prevalence of elevated stress, inflammation, and neurodegenerative diseases, is the most consistent contributing factor in the development of PND. Although young adults are more resilient to PND, such resilience may be weakened in specific groups of young adults with pathophysiological conditions characterized by excessive or chronic stress and inflammation. In this narrative review, we discuss the roles of stress, inflammation, and epigenetic changes in the development of PND and experimental findings demonstrating that the effects of surgery, traumatic brain injury, and the general anesthetic sevoflurane interact to induce persistent dysregulation of the stress response system, inflammation markers, and behavior in young adult male rats and in their future offspring (intergenerational PND). Accelerated neurocognitive decline after general anesthesia/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem that may affect millions of patients each year. Advanced age, with its increasing prevalence of heightened stress, inflammation, and neurodegenerative alterations, is a consistent contributing factor to the development of PND. Although a strong homeostatic reserve in young adults makes them more resilient to PND, animal data suggest that young adults with pathophysiological conditions characterized by excessive stress and inflammation may be vulnerable to PND, and this altered phenotype may be passed to future offspring (intergenerational PND). The purpose of this narrative review of data in the literature and the authors' own experimental findings in rodents is to draw attention to the possibility of intergenerational PND, a new phenomenon which, if confirmed in humans, may unravel a big new population that may be affected by parental PND. In particular, we discuss the roles of stress, inflammation, and epigenetic alterations in the development of PND. We also discuss experimental findings that demonstrate the effects of surgery, traumatic brain injury, and the general anesthetic sevoflurane that interact to induce persistent dysregulation of the stress response system, inflammation markers, and behavior in young adult male rats and in their future offspring who have neither trauma nor anesthetic exposure (i.e., an animal model of intergenerational PND).