Neuroinflammation and Perioperative Neurocognitive Disorders

Abstract

Neuroinflammation has become a key hallmark of neurological complications including perioperative pathologies such as postoperative delirium and longer-lasting postoperative cognitive dysfunction. Dysregulated inflammation and neuronal injury are emerging from clinical studies as key features of perioperative neurocognitive disorders. These findings are paralleled by a growing body of preclinical investigations aimed at better understanding how surgery and anesthesia affect the central nervous system and possibly contribute to cognitive decline. Herein, we review the role of postoperative neuroinflammation and underlying mechanisms in immune-to-brain signaling after peripheral surgery.

Figure.

Schematic overview of mechanisms involved in postoperative neuroinflammation. Surgery activates the innate immune system resulting in release of proinflammatory mediators (cytokines, chemokines, alarmins, eicosanoids, etc) and activation of systemic immunocompetent cells. These processes negatively affect the blood–brain barrier, resulting in endothelial dysfunction and infiltration of peripheral cells/factors into the brain parenchyma. Within the central nervous system, astrocytes and microglia shift from their resting state and contribute to overall neuronal dysfunction and memory function. Harnessing resolution programs as early as the inflammatory response begins may translate into neuroprotective strategies for PND. An example of microglial activation after surgery using CLARITY is provided on the right panel. Scale bar: 150 µm. BDNF indicates brain-derived neurotrophic factor; Ca+, calcium; DAMP, damage-associated molecular pattern; HMGB1, high-mobility group box 1 protein; IL, interleukin; Mω, macrophage; MCP, monocyte chemoattractant protein; PND, perioperative neurocognitive disorder; TNF, tumor necrosis factor.