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From Bench to Bedside: SPMs for Perioperative Neurocognitive Disorders

Grand Rounds with Niccolò Terrando, PhD

In this Grand Rounds presentation, Niccolò Terrando, PhD shares scientific research on the role of specialized pro-resolving mediators (SPMs) in perioperative neurocognitive disorders. Dr. Terrando uses a preclinical mouse model to study postoperative neuroinflammation and elucidate the impact of SPMs in neuroglia activity and modulating memory.

Perioperative neurocognitive disorders (PND) encompass complications like postoperative delirium and longer-lasting postoperative cognitive dysfunction, which often negatively impact recovery in older adults. These complications can lead to significant, long-term morbidity for the patient and overall heightened medical costs for the individual and healthcare system. Dr. Terrando explains that the brain experiences neuroinflammation following peripheral surgery, such as orthopedic, which can be measured using different biomarkers. Further, he provides insights on key risk factors (e.g., advanced age, postoperative complications, multiple operations, etc.) for PND. But what about safe therapeutics to combat neuroinflammation?

Dr. Terrando recaps inflammation resolution, an active process discovered by Dr. Charles Serhan and colleagues, and explains that complete resolution is the ideal outcome following a painful intervention. After differentiating humoral, neural, and cellular immune-to-brain signaling and communication mechanisms, Dr. Terrando shares important preclinical findings from surgery models in mice. A series of studies in mice treated with a specific SPM, aspirin-triggered resolvin D1 (AT-RvD1), has revealed key discoveries on the impact of this SPM on cognitive and neurological outcomes. Specifically, RvD1 was shown to rescue memory decline and prevent neuroinflammation post-surgery (confirmed by hippocampal gene expression changes), in addition to mediating monocytic regulation and systemic anti-inflammatory effects. These findings have been recently expanded into the use of other SPMs like maresin 1 (MaR1), which can also be assayed in human subjects before and after surgery.

Dr. Terrando concludes that, while surgery activates the immune system and leads to neuroinflammation, SPMs actively balance neuro-glia interactions (humoral and neuronal). RvD1 (with other SPMs) prevent postoperative memory dysfunction in preclinical models. In the future, Dr. Terrando envisions immunonutrition interventions that promote inflammation resolution and clinical biomarkers for the perioperative period to boost inflammation-resolution processes.

This Grand Rounds presentation took place in 2018 at Metagenics Institute in Gig Harbor, WA.

Niccolò Terrando, BSc, DIC, PhD is an Associate Professor of Anesthesiology, Assistant Research Professor in Cell Biology and Senior Fellow at the Duke Center for the Study of Aging and Human Development at Duke University in Durham, NC. Dr. Terrando is also Guest Professor at Capital Medical University in Beijing, China and Adjunct Professor at Central South University in Changsha, China. Dr. Terrando completed his Bachelor of Science degree with Honors at Keele University, and completed his PhD at Imperial College London working closely with colleagues at the Kennedy Institute of Rheumatology. Following a postdoctoral fellowship at the University of California, San Francisco in the Department of Anesthesia and Perioperative Care, Niccolò joined the Karolinska Institute in Stockholm, Sweden in the Department of Physiology and Pharmacology before establishing his laboratory at Duke University in the Department of Anesthesiology.

Dr. Terrando’s research and publications are centered on surgery-induced neuroinflammation and perioperative neurocognitive disorders. Using an integrated interdisciplinary and translational approach, Dr. Terrando’s research addresses complex disease processes utilizing clinically relevant models combined with molecular, genetic, physiological and imaging techniques. Ultimately, his research aims to define the underlying mechanisms leading to memory deficits after surgery and to develop safe strategies to resolve neuroinflammation in the perioperative setting.

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