{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:26:36Z","timestamp":1791289596404,"version":"4.3.0"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Neurological and olfactory disturbances are increasingly recognized as potential complications of general anesthesia, particularly in vulnerable populations, such as the elderly, children, and individuals with comorbidities. Recent studies have highlighted the need for tailored anesthetic approaches in these high-risk groups to mitigate potential long-term effects. These disturbances, including postoperative cognitive dysfunction, delirium, and olfactory deficits, often arise from shared pathophysiological mechanisms, such as neuroinflammation, oxidative stress, and disruptions in cerebral perfusion. The olfactory system is particularly susceptible to anesthesia-induced neurotoxicity given its proximity to central nervous system structures and its role in sensory and cognitive processing. Furthermore, the unique regenerative capacity of olfactory neurons may be compromised by prolonged or repeated exposure to anesthetic agents, potentially leading to long-term olfactory dysfunction. Risk factors, such as advanced age, neurodegenerative diseases, diabetes, cardiovascular conditions, genetic predispositions, and the type and duration of anesthesia exposure, further exacerbate these complications. Preventive strategies, including comprehensive preoperative risk assessment, personalized anesthetic protocols based on genetic and physiological profiles, and proactive postoperative care with early intervention programs, are critical for reducing impairments and improving long-term patient outcomes. Emerging evidence highlights the potential role of neuroprotective agents, such as antioxidants and anti-inflammatory therapies, in mitigating the effects of anesthesia-induced neurotoxicity. Longitudinal studies are needed to evaluate the long-term effects of anesthesia on cognitive and sensory health, particularly in high-risk populations. These studies should incorporate advanced neuroimaging techniques and biomarker analysis to elucidate the underlying mechanisms of anesthesia-induced neurological and olfactory disturbances. This narrative review provides a comprehensive overview of the mechanisms, risk factors, and preventive strategies for neurological and olfactory disturbances after general anesthesia and highlights future directions for research to improve patient outcomes. We conducted a comprehensive literature search using databases, such as PubMed and Scopus, to identify relevant studies.<\/jats:p>","DOI":"10.3390\/life15030344","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T10:04:28Z","timestamp":1740391468000},"page":"344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neurological and Olfactory Disturbances After General Anesthesia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-0185","authenticated-orcid":false,"given":"Antonino","family":"Maniaci","sequence":"first","affiliation":[{"name":"Deparment of Medicine and Surgery, University of Enna \u201cKore\u201d, 94019 Enna, Italy"},{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"},{"name":"Division of Laryngology and Bronchoesophagology, Department of Otolaryngology Head Neck Surgery, EpiCURA Hospital, UMONS Research Institute for Health Sciences and Technology, Faculty of Medicine, University of Mons (UMons), 7000 Mons, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8127-5045","authenticated-orcid":false,"given":"Mario","family":"Lentini","sequence":"additional","affiliation":[{"name":"Deparment of Medicine and Surgery, University of Enna \u201cKore\u201d, 94019 Enna, Italy"},{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Trombadore","sequence":"additional","affiliation":[{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loris","family":"Gruppuso","sequence":"additional","affiliation":[{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santo","family":"Milardi","sequence":"additional","affiliation":[{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Scrofani","sequence":"additional","affiliation":[{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5271-1810","authenticated-orcid":false,"given":"Giuseppe","family":"Cuttone","sequence":"additional","affiliation":[{"name":"Deparment of Medicine and Surgery, University of Enna \u201cKore\u201d, 94019 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9331-2788","authenticated-orcid":false,"given":"Massimiliano","family":"Sorbello","sequence":"additional","affiliation":[{"name":"Deparment of Medicine and Surgery, University of Enna \u201cKore\u201d, 94019 Enna, Italy"},{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Modica","sequence":"additional","affiliation":[{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0845-0845","authenticated-orcid":false,"given":"Jerome R.","family":"Lechien","sequence":"additional","affiliation":[{"name":"Division of Laryngology and Bronchoesophagology, Department of Otolaryngology Head Neck Surgery, EpiCURA Hospital, UMONS Research Institute for Health Sciences and Technology, Faculty of Medicine, University of Mons (UMons), 7000 Mons, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-7959","authenticated-orcid":false,"given":"Paolo","family":"Boscolo-Rizzo","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, 34121 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0215-5620","authenticated-orcid":false,"given":"Daniele Salvatore","family":"Patern\u00f2","sequence":"additional","affiliation":[{"name":"Asp 7 Ragusa, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2156-7554","authenticated-orcid":false,"given":"Luigi","family":"La Via","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care, University Hospital Policlinico \u201cG. Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/01.anes.0000296071.19434.1e","article-title":"Predictors of cognitive dysfunction after major noncardiac surgery","volume":"108","author":"Monk","year":"2008","journal-title":"Anesthesiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1213\/ANE.0b013e318215217e","article-title":"Postoperative cognitive dysfunction is independent of type of surgery and anesthetic","volume":"112","author":"Evered","year":"2011","journal-title":"Anesth. Analg."},{"key":"ref_3","first-page":"484","article-title":"Olfactory dysfunction and its measurement in the clinic and workplace","volume":"74","author":"Doty","year":"2001","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_4","unstructured":"Wilson, D.A., and Stevenson, R.J. (2006). Learning to Smell: Olfactory Perception from Neurobiology to Behavior, Johns Hopkins University Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ar.10047","article-title":"Neural regeneration and the peripheral olfactory system","volume":"269","author":"Schwob","year":"2002","journal-title":"Anat. Rec."},{"key":"ref_6","first-page":"1232","article-title":"Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients","volume":"45","author":"Rasmussen","year":"2001","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1097\/ALN.0b013e318195b569","article-title":"Long-term consequences of postoperative cognitive dysfunction","volume":"110","author":"Steinmetz","year":"2009","journal-title":"Anesthesiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0140-6736(13)60688-1","article-title":"Delirium in elderly people","volume":"383","author":"Inouye","year":"2014","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1097\/00000542-200605000-00015","article-title":"The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels","volume":"104","author":"Xie","year":"2006","journal-title":"Anesthesiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/ana.23536","article-title":"Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory","volume":"71","author":"Zhang","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_11","first-page":"1563","article-title":"Olfactory dysfunction after general anesthesia","volume":"21","author":"Haxel","year":"2014","journal-title":"J. Clin. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Doty, R.L., and Kamath, V. (2014). The influences of age on olfaction: A review. Front. Psychol., 5.","DOI":"10.3389\/fpsyg.2014.00020"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ana.21291","article-title":"Association of olfactory dysfunction with risk for future Parkinson\u2019s disease","volume":"63","author":"Ross","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_14","first-page":"3090","article-title":"Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia","volume":"28","author":"Planel","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1017\/S1355617703930116","article-title":"Left hippocampal volume loss in Alzheimer\u2019s disease is reflected in performance on odor identification: A structural MRI study","volume":"9","author":"Murphy","year":"2003","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev-neuro-060909-153200","article-title":"General anesthesia and altered states of arousal: A systems neuroscience analysis","volume":"34","author":"Brown","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_17","first-page":"e818","article-title":"Long-term differences in language and cognitive function after childhood exposure to anesthesia","volume":"134","author":"Ing","year":"2014","journal-title":"Pediatrics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nrn2372","article-title":"General anaesthesia: From molecular targets to neuronal pathways of sleep and arousal","volume":"9","author":"Franks","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1097\/ALN.0000000000002334","article-title":"Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery\u20142018","volume":"129","author":"Evered","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_20","first-page":"328","article-title":"Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: A randomized clinical trial","volume":"154","author":"Deiner","year":"2019","journal-title":"Jpn. Automob. Manuf. Assoc. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/ana.22082","article-title":"Role of interleukin-1\u03b2 in postoperative cognitive dysfunction","volume":"68","author":"Cibelli","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_22","first-page":"1126","article-title":"The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors","volume":"113","author":"Wei","year":"2010","journal-title":"Anesthesiology"},{"key":"ref_23","unstructured":"Mutch, W.A.C., El-Gabalawy, R.M., and Graham, M.R. (2015). Postoperative delirium, learning, and anesthetic neurotoxicity: Some perspectives and directions. Front. Neurol., 6."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1056\/NEJMoa1112923","article-title":"Cognitive trajectories after postoperative delirium","volume":"367","author":"Saczynski","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_25","first-page":"1889","article-title":"The pathophysiology of olfactory dysfunction and its relationship to cerebral perfusion: A study with MRI","volume":"266","author":"Galletti","year":"2009","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S1474-4422(15)00101-5","article-title":"The interface between delirium and dementia in elderly adults","volume":"14","author":"Fong","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_27","first-page":"244","article-title":"Association of delirium with cognitive decline in late life: A neuropathologic study of 3 population-based cohort studies","volume":"74","author":"Davis","year":"2017","journal-title":"Jpn. Automob. Manuf. Assoc. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/bmb\/ldt006","article-title":"The neuroinflammatory response of postoperative cognitive decline","volume":"106","author":"Vacas","year":"2013","journal-title":"Br. Med. Bull."},{"key":"ref_29","first-page":"746","article-title":"Isoflurane-induced apoptosis of neurons and oligodendrocytes in the fetal rhesus macaque brain","volume":"118","author":"Creeley","year":"2013","journal-title":"Anesthesiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1523\/JNEUROSCI.23-03-00876.2003","article-title":"Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits","volume":"23","author":"Hartman","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_31","first-page":"2312","article-title":"Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood","volume":"315","author":"Sun","year":"2014","journal-title":"Jpn. Automob. Manuf. Assoc."},{"key":"ref_32","first-page":"1776","article-title":"The synaptic organization of the brain: An introduction to molecular neuroscience of olfaction","volume":"306","author":"Shepherd","year":"2004","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01206454","article-title":"Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons","volume":"8","author":"Graziadei","year":"1979","journal-title":"J. Neurocytol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Pan, C., Wu, X., Dong, Y., Culley, D.J., Crosby, G., Li, T., and Xie, Z. (2013). Different effects of anesthetic isoflurane on caspase-3 activation in young and aged mice. Front. Cell. Neurosci., 7.","DOI":"10.3389\/fncel.2014.00014"},{"key":"ref_35","first-page":"610","article-title":"Central olfactory processing in health and disease","volume":"43","author":"Wilson","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_36","first-page":"525","article-title":"Olfactory dysfunction after general anesthesia: A case-control study","volume":"27","author":"Haxel","year":"2015","journal-title":"J. Clin. Anesth."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrn2883","article-title":"Central mechanisms of odour object perception","volume":"11","author":"Gottfried","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_38","first-page":"12222","article-title":"Getting to the heart of the matter: Direct visualization of angiogenesis in the olfactory system","volume":"34","author":"Platt","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/EJA.0000000000002069","article-title":"Preoperative assessment of adults undergoing elective noncardiac surgery: Updated guidelines from the European Society of Anaesthesiology and Intensive Care","volume":"42","author":"Lamperti","year":"2025","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_40","first-page":"155","article-title":"Cerebrospinal fluid A\u03b2 to tau ratio and postoperative cognitive change","volume":"259","author":"Xie","year":"2014","journal-title":"Ann. Surg."},{"key":"ref_41","first-page":"618","article-title":"Anesthesia, calcium homeostasis and Alzheimer\u2019s disease","volume":"10","author":"Wei","year":"2013","journal-title":"Curr. Alzheimer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1126\/science.6505700","article-title":"Smell identification ability: Changes with age","volume":"226","author":"Doty","year":"1984","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s00415-008-0807-9","article-title":"The association between smoking and smell and taste impairment in the general population","volume":"255","author":"Vennemann","year":"2008","journal-title":"J. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00405-006-0173-0","article-title":"Normative data for the \u201cSniffin\u2019 Sticks\u201d including tests of odor identification, odor discrimination, and olfactory thresholds: An upgrade based on a group of more than 3,000 subjects","volume":"264","author":"Hummel","year":"2007","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_46","first-page":"499","article-title":"Taste and smell phantoms revealed by brain functional MRI (fMRI)","volume":"27","author":"Henkin","year":"2003","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/ana.21548","article-title":"The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo","volume":"64","author":"Xie","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_48","first-page":"2485","article-title":"The role of inflammation in neuronal injury in the olfactory system","volume":"121","author":"Platt","year":"2011","journal-title":"Laryngoscope"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1213\/ane.0b013e318172ba0a","article-title":"Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain","volume":"106","author":"Cattano","year":"2008","journal-title":"Anesth. Analg."},{"key":"ref_50","first-page":"1","article-title":"Olfactory epithelial changes and inflammatory markers in the nasal mucosa after total laryngectomy","volume":"2","author":"Gudziol","year":"2005","journal-title":"Chemosens. Percept."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lavalle, S., Masiello, E., Iannella, G., Magliulo, G., Pace, A., Lechien, J.R., Calvo-Henriquez, C., Cocuzza, S., Parisi, F.M., and Favier, V. (2024). Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review. Life, 14.","DOI":"10.3390\/life14040425"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1001\/archotol.128.6.635","article-title":"Characteristics of olfactory disorders in relation to major causes of olfactory loss","volume":"128","author":"Temmel","year":"2002","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_53","first-page":"900","article-title":"Age-related effects on the olfactory system","volume":"82","author":"Murphy","year":"2019","journal-title":"Microsc. Res. Tech."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1053\/j.jvca.2010.05.003","article-title":"Postoperative Delirium and Short-Term Cognitive Dysfunction Occur More Frequently in Patients Undergoing Valve Surgery with or without Coronary Artery Bypass Graft Surgery Compared with Coronary Artery Bypass Graft Surgery Alone: Results of a Pilot Study","volume":"25","author":"Hudetz","year":"2011","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_55","first-page":"e01583","article-title":"Genetic susceptibility to olfactory impairment: A genome-wide association study","volume":"10","author":"Jiang","year":"2020","journal-title":"Brain Behav."},{"key":"ref_56","first-page":"765","article-title":"Cerebrospinal fluid biomarker for Alzheimer disease predicts postoperative cognitive dysfunction","volume":"127","author":"Evered","year":"2017","journal-title":"Anesthesiology"},{"key":"ref_57","first-page":"72","article-title":"Cognitive decline after delirium in patients undergoing cardiac surgery","volume":"125","author":"Brown","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.arr.2017.09.001","article-title":"Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition","volume":"40","author":"Calder","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_60","first-page":"CD001159","article-title":"Peripheral nerve blocks for hip fractures","volume":"11","author":"Guay","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1213\/01.ane.0000166974.96219.cd","article-title":"Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia","volume":"101","author":"Casati","year":"2005","journal-title":"Anesth. Analg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/00000542-200008000-00016","article-title":"The effects of increasing plasma concentrations of dexmedetomidine in humans","volume":"93","author":"Ebert","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/lary.20101","article-title":"Effects of olfactory training in patients with olfactory loss","volume":"119","author":"Hummel","year":"2009","journal-title":"Laryngoscope"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/S0140-6736(06)68700-X","article-title":"Persistent postsurgical pain: Risk factors and prevention","volume":"367","author":"Kehlet","year":"2006","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Xiong, W.X., Zhou, G.X., Wang, B., Xue, Z.G., Wang, L., Sun, H.C., and Ge, S.J. (2013). Impaired spatial learning and memory after sevoflurane-nitrous oxide anesthesia in aged rats is associated with down-regulated cAMP\/CREB signaling. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079408"},{"key":"ref_66","first-page":"204","article-title":"Effects of dexmedetomidine, a novel imidazole sedative-anesthetic agent, on adrenal steroidogenesis: In vivo and in vitro studies","volume":"73","author":"Maze","year":"2008","journal-title":"Anesth. Analg."},{"key":"ref_67","first-page":"613","article-title":"The role of immune cells in brain development and neurodevelopmental diseases","volume":"31","author":"Tanabe","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1053\/j.jvca.2008.12.021","article-title":"Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass","volume":"23","author":"Hudetz","year":"2009","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/7854_2012_220","article-title":"All about running: Synaptic plasticity, growth factors and adult hippocampal neurogenesis","volume":"15","author":"Vivar","year":"2013","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/jgs.12794","article-title":"Patterns of surgical care and complications in elderly adults","volume":"62","author":"Deiner","year":"2020","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/ANA.0b013e3182712fba","article-title":"BIS-guided anesthesia decreases postoperative delirium and cognitive decline","volume":"25","author":"Chan","year":"2019","journal-title":"J. Neurosurg. Anesthesiol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/3\/344\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:40:17Z","timestamp":1760028017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/3\/344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,22]]},"references-count":71,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["life15030344"],"URL":"https:\/\/doi.org\/10.3390\/life15030344","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,22]]}}}