title: Extracellular RNAs as a chemical initiator for postoperative cognitive dysfunction.
abstract: Postoperative cognitive dysfunction (POCD) is a common complication that presents in the postoperative stage, especially in elderly patients. Despite years of considerable progress, the detailed molecular mechanisms of POCD remain largely unknown. Neuroinflammation has been increasingly pointed out as one of the core mechanisms for the pathogenesis of POCD. However, application of anti-inflammatory drugs failed to show consistent beneficial effect in patients with cognitive decline. Hence, it might be of great importance to identify the inflammatory initiators that are involved in the mediation, amplification and perpetuation of postoperative neuroinflammatory reactions. Extracellular RNAs (exRNAs), released from necrotic cells, were demonstrated to initiate the inflammatory responses in various pathological conditions. Recent study has suggested neuroprotective and edema protective effects of ribonuclease (RNase), the counterpart of RNA, in acute stroke. It was theorized that RNase acted against endogenous RNA that was released from tissue damage. Similarly, we have observed significant attenuation of cognitive impairment by RNase in aged mice after unilateral nephrectomy. Damping the systemic initiators at early stages may help to prevent the chain reaction that triggers the central inflammatory or apoptotic response. Therefore, we propose the hypothesis that exRNAs released upon stress, through acting on the peripheral and/or central receptors, may trigger a damaging cascade leading to the development of POCD. Undoubtedly, further study is urgently needed to elucidated the exact signaling mechanisms and confirm the proposed hypothesis.
authors: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Chan
authors: C
authors: Chen
authors: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Xu
authors: X
authors: Cheng
authors: Department of Surgical Operating Room, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Ji
authors: J
authors: Li
authors: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Hai
authors: H
authors: Chen
authors: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Shu
authors: S
authors: Zhang
authors: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, MA, USA.
authors: Yuanlin
authors: Y
authors: Dong
authors: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Lu
authors: L
authors: Gan
authors: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Jin
authors: J
authors: Liu
authors: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: xwtao_zhu@yahoo.com.
authors: Tao
authors: T
authors: Zhu
mesh_terms: D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis; D060825:Cognitive Dysfunction / Q000150:complications / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D003693:Delirium / Q000150:complications; D004487:Edema; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000860:Hypoxia; D007113:Immunity, Innate; D007249:Inflammation / Q000150:complications; D051379:Mice; D008962:Models, Theoretical; D011183:Postoperative Complications / Q000209:etiology* / Q000517:prevention & control; D012313:RNA / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D012333:RNA, Messenger; D012313:RNA; D012260:Ribonucleases