Skip to content
2000
Volume 26, Issue 14
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Perioperative Neurocognitive (PND) disorders represent a prevalent complication among geriatric patients, manifested in diverse forms of cognitive impairment following anesthesia and surgical procedures. Even though the exact origin of PND disorders is still unknown, neuroinflammation has been identified as a significant contributing factor, particularly in older patients. Hence, this review aims to provide a deeper insight into the underlying mechanism and associated potent therapeutic targets for the efficient management of perioperative neurocognitive disorders. Many factors, such as PRRs, chemokine receptors, immunoglobulin superfamily receptors, and purinergic receptors, are involved in the development and occurrence of perioperative neurocognitive disorders to varying degrees and may be valuable biomarkers for their effective management. Here, we present a comprehensive overview of the involvement of neuroinflammation in PND disorders, including their onset and possible therapeutic targets. This review would benefit future researchers in elucidating a better therapeutic approach for the management of perioperative neurocognitive disorders. We have also briefly outlined the clinical trials associated with Postoperative neurocognitive disorders in the last section of the review. Altogether, this review would help the researchers investigate better therapeutics for the management of PND disorders.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010315764240920064245
2024-09-26
2025-12-21

  • From This Site

    /content/journals/cpb/10.2174/0113892010315764240920064245
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. RundshagenI. Postoperative cognitive dysfunction.Dtsch. Arztebl. Int.20141118119125 24622758
     [Google Scholar]
  2. LiuY. FuH. WangT. Neuroinflammation in perioperative neurocognitive disorders: From bench to the bedside.CNS Neurosci. Ther.202228448449610.1111/cns.13794 34990087
     [Google Scholar]
  3. SafavyniaS.A. GoldsteinP.A. EveredL.A. Mitigation of perioperative neurocognitive disorders: A holistic approach.Front. Aging Neurosci.20221494914810.3389/fnagi.2022.949148 35966792
     [Google Scholar]
  4. KongH. XuL.M. WangD.X. Perioperative neurocognitive disorders: A narrative review focusing on diagnosis, prevention, and treatment.CNS Neurosci. Ther.20222881147116710.1111/cns.13873 35652170
     [Google Scholar]
  5. EveredL. AtkinsK. SilbertB. ScottD.A. Acute peri‐operative neurocognitive disorders: a narrative review.Anaesthesia202277S1Suppl. 1344210.1111/anae.15613 35001385
     [Google Scholar]
  6. ZhouM. CornellJ. SalinasS. HuangH-Y. Microglia regulation of synaptic plasticity and learning and memory.Neural Regen. Res.202217470571610.4103/1673‑5374.322423 34472455
     [Google Scholar]
  7. RobertsW.K. DarnellR.B. Neuroimmunology of the paraneoplastic neurological degenerations.Curr. Opin. Immunol.200416561662210.1016/j.coi.2004.07.009 15342008
     [Google Scholar]
  8. MaK. BebawyJ.F. HemmerL.B. Multimodal analgesia and intraoperative neuromonitoring.J. Neurosurg. Anesthesiol.202335217217610.1097/ANA.0000000000000904 36662721
     [Google Scholar]
  9. NairV.A. GladstonD.V. KrishnaK.M.J. KoshyR.C. Effects of intravenous dexmedetomidine on perioperative haemodynamics and quality of emergence in patients undergoing head and neck surgery following general anaesthesia—a comparative randomized, double-blind placebo-controlled study.Ain-Shams Journal of Anesthesiology20221414810.1186/s42077‑022‑00248‑9
     [Google Scholar]
  10. NemotoA. GoyagiT. NemotoW. NakagawasaiO. Tan-NoK. NiiyamaY. Low skeletal muscle mass is associated with perioperative neurocognitive disorder due to decreased neurogenesis in rats.Anesth. Analg.20221341194203 34347659
     [Google Scholar]
  11. ParkD. KimB.H. LeeS.E. JeongE. ChoK. ParkJ.K. ChoiY.J. JinS. HongD. KimM.C. Usefulness of intraoperative neurophysiological monitoring during the clipping of unruptured intracranial aneurysm: diagnostic efficacy and detailed protocol.Front. Surg.2021863105310.3389/fsurg.2021.631053 33718428
     [Google Scholar]
  12. VelkersC. BergerM. GillS.S. EckenhoffR. StuartH. WhiteheadM. AustinP.C. RochonP.A. SeitzD. Association between exposure to general versus regional anesthesia and risk of dementia in older adults.J. Am. Geriatr. Soc.2021691586710.1111/jgs.16834 33025584
     [Google Scholar]
  13. JiwajiZ. MárkusN.M. McQueenJ. EmelianovaK. HeX. DandoO. HardinghamG.E. General anesthesia alters CNS and astrocyte expression of activity-dependent and activity-independent genes.Front. Netw. Physiol.20233121636610.3389/fnetp.2023.1216366
     [Google Scholar]
  14. PattersonS.L. Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity.Neuropharmacology201596Pt A111810.1016/j.neuropharm.2014.12.02025549562
     [Google Scholar]
  15. BourgognonJ.M. CavanaghJ. The role of cytokines in modulating learning and memory and brain plasticity.Brain Neurosci. Adv.2020410.1177/2398212820979802 33415308
     [Google Scholar]
  16. SubramaniyanS. TerrandoN. Narrative review article: neuroinflammation and perioperative neurocognitive disorders.Anesth. Analg.2019128478178810.1213/ANE.0000000000004053 30883423
     [Google Scholar]
  17. LuoT.Y. ZhouW. XiangG.F. ZhangY. LiuQ. Identification of perioperative neurocognitive dysfunction biomarkers in cerebrospinal fluid with quantitative proteomic approach in patients undergoing transurethral resection of prostate with combined spinal and epidural analgesia.Medicine (Baltimore)202210136e3044810.1097/MD.0000000000030448 36086739
     [Google Scholar]
  18. NishiboriM. WangD. OusakaD. WakeH. High mobility group box-1 and blood–brain barrier disruption.Cells2020912265010.3390/cells9122650 33321691
     [Google Scholar]
  19. WangZ. ChenW.H. LiS.X. HeZ.M. ZhuW.L. JiY.B. WangZ. ZhuX.M. YuanK. BaoY.P. ShiL. MengS.Q. XueY.X. XieW. ShiJ. YanW. WeiH. LuL. HanY. Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation.Mol. Psychiatry202126116277629210.1038/s41380‑021‑01113‑1 33963281
     [Google Scholar]
  20. YiY.S. Functional crosstalk between non‐canonical caspase‐11 and canonical NLRP3 inflammasomes during infection‐mediated inflammation.Immunology2020159214215510.1111/imm.13134 31630388
     [Google Scholar]
  21. SaxenaS. KruysV. De JonghR. VamecqJ. MazeM. High-mobility group box-1 and its potential role in perioperative neurocognitive disorders.Cells20211010258210.3390/cells10102582 34685561
     [Google Scholar]
  22. ZuoY. YinL. ChengX. LiJ. WuH. LiuX. GuE. WuJ. Elamipretide attenuates pyroptosis and perioperative neurocognitive disorders in aged mice.Front. Cell. Neurosci.20201425110.3389/fncel.2020.00251 32903868
     [Google Scholar]
  23. BiasizzoM. Kopitar-JeralaN. Interplay between NLRP3 inflammasome and autophagy.Front. Immunol.20201159180310.3389/fimmu.2020.591803 33163006
     [Google Scholar]
  24. BecherB. SpathS. GovermanJ. Cytokine networks in neuroinflammation.Nat. Rev. Immunol.2017171495910.1038/nri.2016.123 27916979
     [Google Scholar]
  25. WangH. HeY. SunZ. RenS. LiuM. WangG. YangJ. Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression.J. Neuroinflammation202219113210.1186/s12974‑022‑02492‑0 35668399
     [Google Scholar]
  26. JurgaA.M. PalecznaM. KuterK.Z. Overview of general and discriminating markers of differential microglia phenotypes.Front. Cell. Neurosci.20201419810.3389/fncel.2020.00198 32848611
     [Google Scholar]
  27. ZhangC. KanX. ZhangB. NiH. ShaoJ. The role of triggering receptor expressed on myeloid cells-1 (TREM-1) in central nervous system diseases.Mol. Brain20221518410.1186/s13041‑022‑00969‑w 36273145
     [Google Scholar]
  28. YadavH. Jaldhi; Bhardwaj, R.; Anamika; Bakshi, A.; Gupta, S.; Maurya, S.K. Unveiling the role of gut-brain axis in regulating neurodegenerative diseases: A comprehensive review.Life Sci.202333012202210.1016/j.lfs.2023.122022 37579835
     [Google Scholar]
  29. XuP. ZhangX. LiuQ. XieY. ShiX. ChenJ. LiY. GuoH. SunR. HongY. LiuX. XuG. Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke.Cell Death Dis.201910855510.1038/s41419‑019‑1777‑9 31324751
     [Google Scholar]
  30. HeinzR. SchneiderU.C. TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage (SAH): Potential Targets for Future Anti-Inflammatory Therapies.Int. J. Mol. Sci.202223201261810.3390/ijms232012618 36293468
     [Google Scholar]
  31. JiangW. LiuF. LiH. WangK. CaoX. XuX. ZhouY. ZouJ. ZhangX. CuiX. TREM2 ameliorates anesthesia and surgery-induced cognitive impairment by regulating mitophagy and NLRP3 inflammasome in aged C57/BL6 mice.Neurotoxicology20229021622710.1016/j.neuro.2022.04.005 35447280
     [Google Scholar]
  32. ZhaiQ. LiF. ChenX. JiaJ. SunS. ZhouD. MaL. JiangT. BaiF. XiongL. WangQ. Triggering receptor expressed on myeloid cells 2, a novel regulator of immunocyte phenotypes, confers neuroprotection by relieving neuroinflammation.Anesthesiology201712719811010.1097/ALN.0000000000001628 28398927
     [Google Scholar]
  33. RositoM. TestiC. ParisiG. CorteseB. BaioccoP. Di AngelantonioS. Exploring the use of dimethyl fumarate as microglia modulator for neurodegenerative diseases treatment.Antioxidants20209870010.3390/antiox9080700 32756501
     [Google Scholar]
  34. DubeyD. KieseierB.C. HartungH.P. HemmerB. WarnkeC. MengeT. Miller-LittleW.A. StuveO. Dimethyl fumarate in relapsing–remitting multiple sclerosis: rationale, mechanisms of action, pharmacokinetics, efficacy and safety.Expert Rev. Neurother.201515433934610.1586/14737175.2015.1025755 25800129
     [Google Scholar]
  35. TaoY. LiL. JiangB. FengZ. YangL. TangJ. ChenQ. ZhangJ. TanQ. FengH. ChenZ. ZhuG. Cannabinoid receptor-2 stimulation suppresses neuroinflammation by regulating microglial M1/M2 polarization through the cAMP/PKA pathway in an experimental GMH rat model.Brain Behav. Immun.20165811812910.1016/j.bbi.2016.05.020 27261088
     [Google Scholar]
  36. KucerovaJ. TabiovaK. DragoF. MicaleV. Therapeutic potential of cannabinoids in schizophrenia.Recent Patents CNS Drug Discov.201491132510.2174/1574889809666140307115532 24605939
     [Google Scholar]
  37. LangJ. GaoL. WuJ. MengJ. GaoX. MaH. YanD. Resveratrol attenuated manganese-induced learning and memory Impairments in mice through PGC-1alpha-mediated autophagy and microglial M1/M2 polarization.Neurochem. Res.202247113414342710.1007/s11064‑022‑03695‑w 35871432
     [Google Scholar]
  38. AbaisJ.M. XiaM. LiG. ChenY. ConleyS.M. GehrT.W.B. BoiniK.M. LiP.L. Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury via thioredoxin-interacting protein (TXNIP) during hyperhomocysteinemia.J. Biol. Chem.201428939271592716810.1074/jbc.M114.567537 25138219
     [Google Scholar]
  39. WangM. LinX. YangX. YangY. Research progress on related mechanisms of uric acid activating NLRP3 inflammasome in chronic kidney disease.Ren. Fail.202244161562410.1080/0886022X.2022.2036620 35382689
     [Google Scholar]
  40. DingK. SongC. HuH. YinK. HuangH. TangH. The Role of NLRP3 Inflammasome in Diabetic Cardiomyopathy and Its Therapeutic Implications.Oxid. Med. Cell. Longev.2022202211910.1155/2022/3790721 36111168
     [Google Scholar]
  41. OladapoA. JacksonT. MenolascinoJ. PeriyasamyP. Role of pyroptosis in the pathogenesis of various neurological diseases.Brain Behav. Immun.202411742844610.1016/j.bbi.2024.02.001 38336022
     [Google Scholar]
  42. LiJ. LiL. HeJ. XuJ. BaoF. The NLRP3 inflammasome is a potential mechanism and therapeutic target for perioperative neurocognitive disorders.Front. Aging Neurosci.202314107200310.3389/fnagi.2022.1072003 36688154
     [Google Scholar]
  43. PaudelY.N. AngelopoulouE. PiperiC. BalasubramaniamV.R.M.T. OthmanI. ShaikhM.F. Enlightening the role of high mobility group box 1 (HMGB1) in inflammation: Updates on receptor signalling.Eur. J. Pharmacol.201985817248710.1016/j.ejphar.2019.172487 31229535
     [Google Scholar]
  44. KlegerisA. Regulation of neuroimmune processes by damage- and resolution-associated molecular patterns.Neural Regen. Res.202116342342910.4103/1673‑5374.293134 32985460
     [Google Scholar]
  45. CrowleyT. CryanJ.F. DownerE.J. O’LearyO.F. Inhibiting neuroinflammation: The role and therapeutic potential of GABA in neuro-immune interactions.Brain Behav. Immun.20165426027710.1016/j.bbi.2016.02.001 26851553
     [Google Scholar]
  46. XinY. ChuT. ZhouS. XuA. α5GABAA receptor: A potential therapeutic target for perioperative neurocognitive disorders, a review of preclinical studies.Brain Res. Bull.202320511082110.1016/j.brainresbull.2023.110821 37984621
     [Google Scholar]
  47. ZhangY. ChenH. ZhangW. CaiY. ShanP. WuD. ZhangB. LiuH. KhanZ.A. LiangG. Arachidonic acid inhibits inflammatory responses by binding to myeloid differentiation factor-2 (MD2) and preventing MD2/toll-like receptor 4 signaling activation.Biochim. Biophys. Acta Mol. Basis Dis.20201866516568310.1016/j.bbadis.2020.165683 31953218
     [Google Scholar]
  48. ZuoW. ZhaoJ. ZhangJ. FangZ. DengJ. FanZ. GuoY. HanJ. HouW. DongH. XuF. XiongL. MD2 contributes to the pathogenesis of perioperative neurocognitive disorder via the regulation of α5GABAA receptors in aged mice.J. Neuroinflammation202118120410.1186/s12974‑021‑02246‑4
     [Google Scholar]
  49. WhiteheadL. BrownG.D. Pattern recognition receptors and inflammation.Cell201714080582010.1002/9783527692156.ch8
     [Google Scholar]
  50. TangCC LiuDX ZhuZQ Research progress of microglial surface receptors in perioperative neurocognitive disorders.Ibrain2023ibra.1213610.1002/ibra.12136
     [Google Scholar]
  51. SunH. HuH. XuX. FangM. TaoT. LiangZ. Protective effect of dexmedetomidine in cecal ligation perforation-induced acute lung injury through HMGB1/RAGE pathway regulation and pyroptosis activation.Bioengineered2021122106081062310.1080/21655979.2021.2000723 34747306
     [Google Scholar]
  52. HuX. LiouA.K.F. LeakR.K. XuM. AnC. SuenagaJ. ShiY. GaoY. ZhengP. ChenJ. Neurobiology of microglial action in CNS injuries: Receptor-mediated signaling mechanisms and functional roles.Prog. Neurobiol.2014119-120608410.1016/j.pneurobio.2014.06.002 24923657
     [Google Scholar]
  53. TurbicA. LeongS.Y. TurnleyA.M. Chemokines and inflammatory mediators interact to regulate adult murine neural precursor cell proliferation, survival and differentiation.PLoS One201169e2540610.1371/journal.pone.0025406 21966521
     [Google Scholar]
  54. FengX. ValdearcosM. UchidaY. LutrinD. MazeM. KoliwadS.K. Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice.JCI Insight201727e9122910.1172/jci.insight.91229 28405620
     [Google Scholar]
  55. ChengC. WanH. CongP. HuangX. WuT. HeM. ZhangQ. XiongL. TianL. Targeting neuroinflammation as a preventive and therapeutic approach for perioperative neurocognitive disorders.J. Neuroinflammation202219129710.1186/s12974‑022‑02656‑y 36503642
     [Google Scholar]
  56. BallazS. The unappreciated roles of the cholecystokinin receptor CCK(1) in brain functioning.Rev. Neurosci.201728657358510.1515/revneuro‑2016‑0088 28343167
     [Google Scholar]
  57. LubbersT. KoxM. de HaanJ.J. GreveJ.W. PompeJ.C. RamakersB.P. PickkersP. BuurmanW.A. Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model.Crit. Care Med.20134151258126510.1097/CCM.0b013e31827c0a17 23388517
     [Google Scholar]
  58. LvG. WangW. SunM. WangF. MaY. LiC. Inhibiting specificity protein 1 attenuated sevoflurane-induced mitochondrial stress and promoted autophagy in hippocampal neurons through PI3K/Akt/mTOR and α7-nAChR signaling.Neurosci. Lett.202379413699510.1016/j.neulet.2022.136995 36464148
     [Google Scholar]
  59. NiH. LiuM. CaoM. ZhangL. ZhaoY. YiL. LiY. LiuL. WangP. DuQ. ZhouH. DongY. Sinomenine regulates the cholinergic anti-inflammatory pathway to inhibit TLR4/NF-κB pathway and protect the homeostasis in brain and gut in scopolamine-induced Alzheimer’s disease mice.Biomed. Pharmacother.202417111619010.1016/j.biopha.2024.116190 38278026
     [Google Scholar]
  60. UddinM.S. Al MamunA. KabirM.T. AshrafG.M. Bin-JumahM.N. Abdel-DaimM.M. Multi-target drug candidates for multifactorial Alzheimer’s disease: AChE and NMDAR as molecular targets.Mol. Neurobiol.202158128130310.1007/s12035‑020‑02116‑9 32935230
     [Google Scholar]
  61. WangF.C. PeiJ.X. ZhuJ. ZhouN.J. LiuD.S. XiongH.F. LiuX.Q. LinD.J. XieY. Overexpression of HMGB1 A-box reduced lipopolysaccharide-induced intestinal inflammation via HMGB1/TLR4 signaling in vitro.World J. Gastroenterol.201521257764777610.3748/wjg.v21.i25.7764 26167076
     [Google Scholar]
  62. YangC. SunS. ZhangQ. GuoJ. WuT. LiuY. YangM. ZhangY. PengY. Exosomes of antler mesenchymal stem cells improve postoperative cognitive dysfunction in cardiopulmonary bypass rats through inhibiting the TLR2/TLR4 signaling pathway.Stem Cells Int.2020202011310.1155/2020/2134565 32300366
     [Google Scholar]
  63. JiangY. ZhangJ. ShiC. LiX. JiangY. MaoR. NF- κ B: a mediator that promotes or inhibits angiogenesis in human diseases?Expert Rev. Mol. Med.202325e2510.1017/erm.2023.20
     [Google Scholar]
  64. SaxenaS. JoostenA. MazeM. Brain Fog: Are clearer skies on the horizon? a review of perioperative neurocognitive disorders. Ann. Update. Int. Care.Emerg. Med.2019201942343010.1007/978‑3‑030‑06067‑1_33
     [Google Scholar]
  65. SaxenaS. RodtsC. NuyensV. LazaronJ. SosnowskiV. VerdonkF. SeidelL. AlbertA. BoogaertsJ. KruysV. MazeM. VamecqJ. Preoperative sedentary behavior is neither a risk factor for perioperative neurocognitive disorders nor associated with an increase in peripheral inflammation, a prospective observational cohort study.BMC Anesthesiol.202020128410.1186/s12871‑020‑01200‑w 33187477
     [Google Scholar]
  66. HumeidanM.L. ReyesJ.P.C. Mavarez-MartinezA. RoethC. NguyenC.M. SheridanE. Zuleta-AlarconA. OteyA. Abdel-RasoulM. BergeseS.D. Effect of cognitive prehabilitation on the incidence of postoperative delirium among older adults undergoing major noncardiac surgery: the neurobics randomized clinical trial.JAMA Surg.2021156214815610.1001/jamasurg.2020.4371 33175114
     [Google Scholar]
  67. EertmansW. De DeyneC. GenbruggeC. MarcusB. BounebS. BeranM. FretT. GutermannH. BoerW. Vander LaenenM. HeylenR. MesottenD. VanelderenP. JansF. Association between postoperative delirium and postoperative cerebral oxygen desaturation in older patients after cardiac surgery.Br. J. Anaesth.2020124214615310.1016/j.bja.2019.09.042 31862160
     [Google Scholar]
  68. BergerM. BrowndykeJ.N. Cooter WrightM. NobuharaC. ReeseM. AckerL. BullockW.M. ColinB.J. DevinneyM.J. MorettiE.W. MoulJ.W. OhlendorfB. LaskowitzD.T. WaligorskaT. ShawL.M. WhitsonH.E. CohenH.J. MathewJ.P. Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers.Ann. Clin. Transl. Neurol.20229215517010.1002/acn3.51499 35104057
     [Google Scholar]
  69. DeinerS. LuoX. LinH.M. SesslerD.I. SaagerL. SieberF.E. LeeH.B. SanoM. JankowskiC. BergeseS.D. CandiottiK. FlahertyJ.H. AroraH. ShanderA. RockP. Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial.JAMA Surg.20171528e171505e17150510.1001/jamasurg.2017.1505 28593326
     [Google Scholar]
/content/journals/cpb/10.2174/0113892010315764240920064245
Loading
Correlation of Neuroinflammation and Therapeutic Targets in Perioperative Neurocognitive Disorders
Current Pharmaceutical Biotechnology 26, 2310 (2025); https://doi.org/10.2174/0113892010315764240920064245
/content/journals/cpb/10.2174/0113892010315764240920064245
/content/journals/cpb/10.2174/0113892010315764240920064245
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): central nervous system; cognitive impairment; Neuroinflammation; PND disorders; signaling pathways; targeted therapeutics

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test