Targeting neuroinflammation as a preventive and therapeutic approach for perioperative neurocognitive disorders

Abstract

Perioperative neurocognitive disorders (PND) is a common postoperative complication associated with regional or general anesthesia and surgery. Growing evidence in both patient and animal models of PND suggested that neuroinflammation plays a critical role in the development and progression of this problem, therefore, mounting efforts have been made to develop novel therapeutic approaches for PND by targeting specific factors or steps alongside the neuroinflammation. Multiple studies have shown that perioperative anti-neuroinflammatory strategies via administering pharmacologic agents or performing nonpharmacologic approaches exert benefits in the prevention and management of PND, although more clinical evidence is urgently needed to testify or confirm these results. Furthermore, long-term effects and outcomes with respect to cognitive functions and side effects are needed to be observed. In this review, we discuss recent preclinical and clinical studies published within a decade as potential preventive and therapeutic approaches targeting neuroinflammation for PND.

Keywords: Neuroinflammation; Perioperative neurocognitive disorders; Postoperative cognitive dysfunction; Prevention; Treatment.

Fig. 1

From systemic inflammation towards neuroinflammation. Trauma of surgery and administration of anesthesia induced systematic response, resulting in an increased production and release of proinflammatory mediators (dots in blue). Surgeries induced accumulation of CCR2-expressing macrophages in hippocampi, then upregulated CCL2 in activated astrocytes and CCR2 in activated microglia, which could be abolished by CCR2 antagonist. The vagus nerve was conducted to release ACh, which binds to ɑ7nAChR and reduce the production of proinflammatory cytokines. The vagal anti-inflammatory reflex could be activated by enteral administration of boluses of lipid and protein enriched nutrition, which could stimulate CCK-1R in the gut to activate the vagal afferent nerves to inhibit proinflammatory cytokine release. Meanwhile, silencing specific protein 1 or ɑ7nAChR agonists exert beneficial effects via reactivating cholinergic anti-inflammatory pathway. The brain mast cell stabilizers are capable of attenuating POCD via inhibiting astrocyte activation and microglia-astrocyte communication. Enteral administration of lipid and protein enriched nutrition has been reported to prevent PND via vagal anti-inflammatory reflex, besides, microbiome-based treatments including nutrition supplementation, prebiotics and SCFAs exert modulatory effects through the Gut-Brain Axis