title: Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.
abstract: Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane. They were tested by Barnes maze and fear conditioning from 2weeks after the surgery. Hippocampus was harvested 6h, 24h and 7days after the surgery for immunohistochemical staining and Western blotting. Mice with surgery under anesthesia with isoflurane, sevoflurane or desflurane took longer than control mice to identify the target box 1 or 8days after the training sessions in Barnes maze. Mice anesthetized by isoflurane or sevoflurane, but not by desflurane, had less freezing behavior than control mice in fear conditioning test. Mice with surgery and anesthesia had increased ionized calcium binding adapter molecule 1 and interleukin 1β in the hippocampus but this increase was smaller in mice anesthetized with desflurane than mice anesthetized with isoflurane. Mice with surgery had increased P2X7 receptors and its downstream molecule caspase 1. Inhibition or knockout of P2X7 receptors attenuated surgery and anesthesia-induced neuroinflammation and cognitive impairment. We conclude that surgery under desflurane anesthesia may have reduced neuroinflammation and cognitive impairment compared with surgery under isoflurane anesthesia. P2X7 receptors may mediate the neuroinflammation and cognitive impairment after surgery.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA; Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA; Department of Anesthesiology and State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, China.
authors.forename: Renchun
authors.initials: R
authors.lastname: Lai
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA; Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China. Electronic address: zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D018685:Anesthetics, Inhalation / Q000627:therapeutic use; D000818:Animals; D002339:Carotid Arteries / Q000601:surgery*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism*; D000077335:Desflurane; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007530:Isoflurane / Q000031:analogs & derivatives / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D014656:Vascular Surgical Procedures / Q000009:adverse effects*
chemical_list: D018685:Anesthetics, Inhalation; D053583:Interleukin-1beta; D058486:Receptors, Purinergic P2X7; D000077335:Desflurane; D007530:Isoflurane
keywords: Learning and memory; Neuroinflammation; P2X7 receptors; Volatile anesthetics