| Summary: | Trauma experienced during surgery can contribute to the development of a systemic inflammatory response that can cause multi-organ dysfunction or even failure. Post-surgical neuroinflammation is a documented phenomenon that results in synaptic impairment, neuronal dysfunction and death, and impaired neurogenesis. Various pro-inflammatory cytokines, such as TNFα, maintain a state of chronic neuroinflammation, manifesting as post-operative cognitive dysfunction and post-operative delirium. Furthermore, elderly patients with post-operative cognitive dysfunction or delirium are three times more likely to experience permanent cognitive impairment or dementia. We conducted a narrative review, considering evidence extracted from various databases including Pubmed, MEDLINE and EMBASE, as well as journals and book reference lists. We found that further pre-clinical and well-powered clinical studies are required to delineate the precise pathogenesis of post-operative delirium and cognitive dysfunction. Despite the burden of post-operative neurological sequelae, clinical studies investigating therapeutic agents, such as dexmedetomidine, ibuprofen and statins, have yielded conflicting results. In addition, evidence supporting novel therapeutic avenues, such as nicotinic and HMGB-1 targeting and remote ischaemic pre-conditioning, is limited and necessitates further investigation. Keywords: Inflammation, Neuroinflammation, Surgery, Systemic inflammatory response syndrome, Multiple organ dysfunction syndrome, Therapeutic targets
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