2016 DIG Research Project | “The Systemic Milieu and its Role in Postoperative Cognitive Dysfunction”
Dr. Niccolò Terrando is originally from the countryside of Torino, Italy. After high school, he moved to the U.K., reading for a dual honors degree in neuroscience and biochemistry (B.S. with honors) at Keele University. He received his Ph.D. from Imperial College London (D.I.C.) working at Chelsea and Westminster Hospital and the Kennedy Institute of Rheumatology under the mentorship of professors Mervyn Maze, Sir Marc Feldmann and Claudia Monaco. As a graduate student, he developed a strong focus on inflammation as a putative factor in the etiology of postoperative cognitive dysfunction (POCD), which remains a key interest in his current research on surgery-induced cognitive decline.
He completed his postdoctoral training at the University of California, San Francisco (UCSF), studying the signaling between peripheral inflammation and memory dysfunction, focusing specifically on macrophage activity and blood-brain barrier disruption after surgery. In 2012, he moved to the Karolinska Institute in Stockholm, Sweden as an assistant professor and explored the role of specialized pro-resolving mediators in neuroinflammation and POCD. In collaboration with the European Society of Anesthesiology, he also developed a program on the effects of general anesthesia on the developing brain in collaboration with several investigators throughout Europe.
In 2015, he moved back to the United States to join the Department of Anesthesiology at Duke University and establish the Perioperative Neurocognitive Outcomes laboratory. Dr. Terrando says Duke Anesthesiology created a unique opportunity to bridge basic science with pioneering clinical research in the context of postoperative neurocognitive outcomes. He believes this innovative, collaborative, multidisciplinary environment is shaping the future of anesthesiology and perioperative medicine.
According to Dr. Terrando, cognitive decline following hospitalization and critical illness is a leading cause of functional impairment worldwide, especially among a rapidly growing, aging population. Up to three quarters of his patients suffer from memory deficits after surgery, which associate with significantly higher mortality rates and prolonged functional disabilities. Emerging evidence from both human and animal studies highlights an association between surgery and long-term neurocognitive impairments, making POCD a major public health issue.
To begin addressing the pathogenesis of anesthesia and surgery-induced cognitive decline, Dr. Terrando and his team developed an orthopedic surgical model in rodents and described a key role of the innate immune response, including pro-inflammatory cytokines and alarmins in mediating neuroinflammation and cognitive decline. Through modulation of anti-inflammatory and pro-resolving mechanisms, they have been able to limit neuroinflammation, restoring cognitive function in preclinical models. Although clinical trials are beginning to evaluate neuroinflammatory changes in patients after surgery, the mechanisms underlying POCD remain controversial and without effective treatment.
The DREAM Innovator Grant will help Dr. Terrando further understand how peripheral surgical trauma contributes to the processes of neuroinflammation and memory dysfunction. Through the support of the DREAM Campaign, he will foster a multidisciplinary approach to establish novel methodologies in understanding how the brain is affected by anesthesia and surgery. These initial data will provide the basis for an application to the National Institutes of Health. Dr. Terrando’s long-term goal is to identify relevant targets in the pathogenesis of POCD and develop safe and effective therapeutics. This will help his team translate these findings into novel clinical trials and improve personalized care.