Neuroinflammation After Surgery: from Mechanisms to Therapeutic Targets

Overview

Journal Nat Immunol

Date 2020 Oct 20

PMID 33077953

Citations 98

Authors

Ting Yang

Ravikanth Velagapudi

Niccolo Terrando

Affiliations

Soon will be listed here.

Abstract

Injury is a key driver of inflammation, a critical yet necessary response involving several mediators that is aimed at restoring tissue homeostasis. Inflammation in the central nervous system can be triggered by a variety of stimuli, some intrinsic to the brain and others arising from peripheral signals. Fine-tuned regulation of this response is crucial in a system that is vulnerable due to, for example, aging and ongoing neurodegeneration. In this context, seemingly harmless interventions like a common surgery to repair a broken limb can overwhelm the immune system and become the driver of further complications such as delirium and other perioperative neurocognitive disorders. Here, we discuss potential mechanisms by which the immune system affects the central nervous system after surgical trauma. Together, these neuroimmune interactions are becoming hallmarks of and potential therapeutic targets for multiple neurologic conditions, including those affecting the perioperative space.

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References

Pluvinage J, Wyss-Coray T . Systemic factors as mediators of brain homeostasis, ageing and neurodegeneration. Nat Rev Neurosci. 2020; 21(2):93-102. DOI: 10.1038/s41583-019-0255-9. View

Soares H, Hicks R, Smith D, McIntosh T . Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury. J Neurosci. 1995; 15(12):8223-33. PMC: 6577921. View

Gelderblom M, Leypoldt F, Steinbach K, Behrens D, Choe C, Siler D . Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke. 2009; 40(5):1849-57. DOI: 10.1161/STROKEAHA.108.534503. View

Evered L, Eckenhoff R . Perioperative cognitive disorders. Response to: Postoperative delirium portends descent to dementia. Br J Anaesth. 2017; 119(6):1241. DOI: 10.1093/bja/aex404. View

Evered L, Silbert B . Postoperative Cognitive Dysfunction and Noncardiac Surgery. Anesth Analg. 2018; 127(2):496-505. DOI: 10.1213/ANE.0000000000003514. View

Rasmussen L, Johnson T, Kuipers H, Kristensen D, Siersma V, Vila P . Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand. 2003; 47(3):260-6. DOI: 10.1034/j.1399-6576.2003.00057.x. View

Inouye S, Westendorp R, Saczynski J . Delirium in elderly people. Lancet. 2013; 383(9920):911-22. PMC: 4120864. DOI: 10.1016/S0140-6736(13)60688-1. View

Koster S, Hensens A, Schuurmans M, van der Palen J . Consequences of delirium after cardiac operations. Ann Thorac Surg. 2011; 93(3):705-11. DOI: 10.1016/j.athoracsur.2011.07.006. View

Robinson T, Raeburn C, Tran Z, Angles E, Brenner L, Moss M . Postoperative delirium in the elderly: risk factors and outcomes. Ann Surg. 2008; 249(1):173-8. DOI: 10.1097/SLA.0b013e31818e4776. View

10.

Marcantonio E, Flacker J, Michaels M, Resnick N . Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc. 2000; 48(6):618-24. DOI: 10.1111/j.1532-5415.2000.tb04718.x. View

11.

Inouye S, Marcantonio E, Kosar C, Tommet D, Schmitt E, Travison T . The short-term and long-term relationship between delirium and cognitive trajectory in older surgical patients. Alzheimers Dement. 2016; 12(7):766-75. PMC: 4947419. DOI: 10.1016/j.jalz.2016.03.005. View

12.

Saczynski J, Marcantonio E, Quach L, Fong T, Gross A, Inouye S . Cognitive trajectories after postoperative delirium. N Engl J Med. 2012; 367(1):30-9. PMC: 3433229. DOI: 10.1056/NEJMoa1112923. View

13.

Davis D, Muniz-Terrera G, Keage H, Stephan B, Fleming J, Ince P . Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies. JAMA Psychiatry. 2017; 74(3):244-251. PMC: 6037291. DOI: 10.1001/jamapsychiatry.2016.3423. View

14.

Fong T, Jones R, Shi P, Marcantonio E, Yap L, Rudolph J . Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009; 72(18):1570-5. PMC: 2677515. DOI: 10.1212/WNL.0b013e3181a4129a. View

15.

Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri C . The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013; 9(1):63-75.e2. DOI: 10.1016/j.jalz.2012.11.007. View

16.

Fick D, Agostini J, Inouye S . Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2002; 50(10):1723-32. DOI: 10.1046/j.1532-5415.2002.50468.x. View

17.

Lee H, Oldham M, Sieber F, Oh E . Impact of Delirium After Hip Fracture Surgery on One-Year Mortality in Patients With or Without Dementia: A Case of Effect Modification. Am J Geriatr Psychiatry. 2016; 25(3):308-315. PMC: 6197860. DOI: 10.1016/j.jagp.2016.10.008. View

18.

Kotfis K, Roberson S, Wilson J, Dabrowski W, Pun B, Wesley Ely E . COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020; 24(1):176. PMC: 7186945. DOI: 10.1186/s13054-020-02882-x. View

19.

Leslie D, Marcantonio E, Zhang Y, Leo-Summers L, Inouye S . One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008; 168(1):27-32. PMC: 4559525. DOI: 10.1001/archinternmed.2007.4. View

20.

Fong T, Davis D, Growdon M, Albuquerque A, Inouye S . The interface between delirium and dementia in elderly adults. Lancet Neurol. 2015; 14(8):823-832. PMC: 4535349. DOI: 10.1016/S1474-4422(15)00101-5. View