Niccolo Terrando, D.I.C., Ph.D. - Associate Professor in Anesthesiology
Assistant Research Professor in Cell Biology
Duke University Medical Center
Perioperative neurocognitive disorders (PND), including acute postoperative delirium and longer-lasting postoperative cognitive dysfunction, are quintessential geriatric complications that affects up to 60% of older adults (1). Orthopedic surgery is a routine procedure in frail and elderly patients, often resulting in high incidence of PND, thus contributing to adverse events and poorer outcomes. To understand the pathophysiology of these complications we have developed a clinically relevant mouse model of orthopedic surgery consisting of an intramedullary fixation of the tibia under general anesthesia to evaluate the impact of aseptic trauma on the central nervous system (2). Using this model we uncovered a link between peripheral cytokines and neuroinflammation in leading to cognitive deficits (3-5). We also identified the role of blood-brain barrier opening and macrophage infiltration as being pivotal for the development of postoperative neuroinflammation and ensuing hippocampal-dependent memory dysfunction (6). Harnessing inflammatory-resolving pathways, for example via cholinergic modulation or specialized pro-resolving lipid mediators, dampen glia activation in response to surgical trauma and curtail the cognitive decline that follows (7-8). Similar pathological hallmarks of blood-brain barrier opening, monocytic infiltration in the cerebrospinal fluid, and microglia reactivity are now observed in patients after non-neurological surgery (9). This suggests a possible role, and putative targeting, of these processes in the pathogenesis of PND.
Oct 28, 2019 @ 4:00 p.m.
Medical Center | K-207 (2-6408)