title: Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice.
abstract: Surgery can induce cognitive decline, a risk that increases with advancing age. In rodents, postoperative cognitive decline (POCD) is associated with the inflammatory activation of hippocampal microglia. To examine the role of microglia in POCD, we inhibited the colony-stimulating factor 1 receptor (CSF1R) in adult mice, effectively depleting CNS microglia. Surgical trauma (tibial fracture) reduced the ability of mice to remember a conditioned response learned preoperatively, a deficit more pronounced and persistent in mice with diet-induced obesity (DIO). Whereas microglial depletion by itself did not affect learning or memory, perioperative microglial depletion remarkably protected mice, including those with DIO, from POCD. This protection was associated with reduced hippocampal levels of inflammatory mediators, abrogation of hippocampal recruitment of CCR2+leukocytes, and higher levels of circulating inflammation-resolving factors. Targeting microglia may thus be a viable strategy to mitigate the development of POCD, particularly in those with increased vulnerability.
authors.affiliation: Department of Anesthesia and Perioperative Care.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Feng
authors.affiliation: The Diabetes Center.
authors.forename: Martin
authors.initials: M
authors.lastname: Valdearcos
authors.affiliation: Department of Anesthesia and Perioperative Care.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Anesthesia and Perioperative Care.
authors.forename: David
authors.initials: D
authors.lastname: Lutrin
authors.affiliation: Department of Anesthesia and Perioperative Care.
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.affiliation: The Diabetes Center.|Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Suneil K
authors.initials: SK
authors.lastname: Koliwad
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005239:Fear; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D044045:Lipoxins / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000473:pathology; D009930:Organic Chemicals / Q000494:pharmacology; D011183:Postoperative Complications / Q000523:psychology*; D054390:Receptors, CCR2 / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D013978:Tibial Fractures / Q000601:surgery
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C515335:Ccr2 protein, mouse; C000604004:Csf1r protein, mouse; D044045:Lipoxins; D009930:Organic Chemicals; C000630231:PLX5622; D054390:Receptors, CCR2; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C040527:lipoxin A4