Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Neuropharmacology
  4. Volume 23, Issue 4
  5. Article
Volume 23, Issue 4
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Sepsis-associated encephalopathy (SAE) is a form of cognitive and psychological impairment resulting from sepsis, which occurs without any central nervous system infection or structural brain injury. Patients may experience long-term cognitive deficits and psychiatric disorders even after discharge. However, the underlying mechanism remains unclear. As cognitive function and mental disease are closely related to synaptic plasticity, it is presumed that alterations in synaptic plasticity play an essential role in the pathological process of SAE. Here, we present a systematic description of the pathogenesis of SAE, which is primarily driven by glial cell activation and subsequent release of inflammatory mediators. Additionally, we elucidate the alterations in synaptic plasticity that occur during SAE and comprehensively discuss the roles played by glial cells and inflammatory factors in this process. In this review, we mainly discuss the synaptic plasticity of SAE, and the main aim is to show the consequences of SAE on inflammatory factors and how they affect synaptic plasticity. This review may enhance our understanding of the mechanism underlying cognitive dysfunction and provide valuable insights into identifying appropriate therapeutic targets for SAE.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/1570159X23666241028105746
2024-10-28
2025-04-11

  • From This Site

    /content/journals/cn/10.2174/1570159X23666241028105746
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SingerM. DeutschmanC.S. SeymourC.W. Shankar-HariM. AnnaneD. BauerM. BellomoR. BernardG.R. ChicheJ.D. CoopersmithC.M. HotchkissR.S. LevyM.M. MarshallJ.C. MartinG.S. OpalS.M. RubenfeldG.D. van der PollT. VincentJ.L. AngusD.C. The third international consensus definitions for sepsis and septic shock (sepsis-3).JAMA2016315880181010.1001/jama.2016.0287 26903338
     [Google Scholar]
  2. GoftonT.E. YoungG.B. Sepsis-associated encephalopathy.Nat. Rev. Neurol.201281055756610.1038/nrneurol.2012.183 22986430
     [Google Scholar]
  3. RobbaC. CrippaI.A. TacconeF.S. Septic encephalopathy.Curr. Neurol. Neurosci. Rep.201818128210.1007/s11910‑018‑0895‑6 30280261
     [Google Scholar]
  4. BarichelloT. SayanaP. GiridharanV.V. ArumanayagamA.S. NarendranB. DellaG.A. PetronilhoF. QuevedoJ. Dal-PizzolF. Long-term cognitive outcomes after sepsis: A translational systematic review.Mol. Neurobiol.201956118625110.1007/s12035‑018‑1048‑2 29687346
     [Google Scholar]
  5. IwashynaT.J. ElyE.W. SmithD.M. LangaK.M. Long-term cognitive impairment and functional disability among survivors of severe sepsis.JAMA2010304161787179410.1001/jama.2010.1553 20978258
     [Google Scholar]
  6. MuzambiR. BhaskaranK. SmeethL. BrayneC. ChaturvediN. Warren-GashC. Assessment of common infections and incident dementia using UK primary and secondary care data: A historical cohort study.Lancet Healthy Longev.202127e426e43510.1016/S2666‑7568(21)00118‑5 34240064
     [Google Scholar]
  7. FritzeT. DoblhammerG. WidmannC.N. HenekaM.T. Time course of dementia following sepsis in German health claims data.Neurol. Neuroimmunol. Neuroinflamm.202181e91110.1212/NXI.0000000000000911 33293458
     [Google Scholar]
  8. HellJ.W. Binding of CaMKII to the NMDA receptor is sufficient for long-term potentiation.Sci. Signal.202316808eadk922410.1126/scisignal.adk9224 37874884
     [Google Scholar]
  9. MageeJ.C. GrienbergerC. Synaptic plasticity forms and functions.Annu. Rev. Neurosci.20204319511710.1146/annurev‑neuro‑090919‑022842 32075520
     [Google Scholar]
  10. TakeuchiT. DuszkiewiczA.J. MorrisR.G.M. The synaptic plasticity and memory hypothesis: encoding, storage and persistence.Philos. Trans. R. Soc. Lond. B Biol. Sci.201436916332013028810.1098/rstb.2013.0288 24298167
     [Google Scholar]
  11. WhitlockJ.R. HeynenA.J. ShulerM.G. BearM.F. Learning induces long-term potentiation in the hippocampus.Science200631357901093109710.1126/science.1128134 16931756
     [Google Scholar]
  12. MazeraudA. RighyC. BouchereauE. BenghanemS. BozzaF.A. SharsharT. Septic-associated encephalopathy: A comprehensive review.Neurotherapeutics202017239240310.1007/s13311‑020‑00862‑1 32378026
     [Google Scholar]
  13. CatarinaA.V. BranchiniG. BettoniL. De OliveiraJ.R. NunesF.B. Sepsis-associated encephalopathy: from pathophysiology to progress in experimental studies.Mol. Neurobiol.20215862770277910.1007/s12035‑021‑02303‑2 33495934
     [Google Scholar]
  14. LiY. YinL. FanZ. SuB. ChenY. MaY. ZhongY. HouW. FangZ. ZhangX. Microglia: A potential therapeutic target for sepsis-associated encephalopathy and sepsis-associated chronic pain.Front. Pharmacol.20201160042110.3389/fphar.2020.600421 33329005
     [Google Scholar]
  15. XinY. TianM. DengS. LiJ. YangM. GaoJ. PeiX. WangY. TanJ. ZhaoF. GaoY. GongY. The key drivers of brain injury by systemic inflammatory responses after sepsis: microglia and neuroinflammation.Mol. Neurobiol.20236031369139010.1007/s12035‑022‑03148‑z 36445634
     [Google Scholar]
  16. ReyesE.P. AbarzúaS. MartinA. RodríguezJ. CortésP.P. FernándezR. LPS-induced c-Fos activation in NTS neurons and plasmatic cortisol increases in septic rats are suppressed by bilateral carotid chemodenervation.Adv. Exp. Med. Biol.201275818519010.1007/978‑94‑007‑4584‑1_26 23080161
     [Google Scholar]
  17. ManabeT. HenekaM.T. Cerebral dysfunctions caused by sepsis during ageing.Nat. Rev. Immunol.202222744445810.1038/s41577‑021‑00643‑7 34764472
     [Google Scholar]
  18. HeH. GengT. ChenP. WangM. HuJ. KangL. SongW. TangH. NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation.Sci. Rep.2016612771110.1038/srep27711 27270556
     [Google Scholar]
  19. ShulyatnikovaT. VerkhratskyA. Astroglia in sepsis associated encephalopathy.Neurochem. Res.2020451839910.1007/s11064‑019‑02743‑2 30778837
     [Google Scholar]
  20. YanX. YangK. XiaoQ. HouR. PanX. ZhuX. Central role of microglia in sepsis-associated encephalopathy: From mechanism to therapy.Front. Immunol.20221392931610.3389/fimmu.2022.929316 35958583
     [Google Scholar]
  21. CecconiM. EvansL. LevyM. RhodesA. Sepsis and septic shock.Lancet201839210141758710.1016/S0140‑6736(18)30696‑2 29937192
     [Google Scholar]
  22. VachharajaniV. CunninghamC. YozaB. CarsonJ.Jr VachharajaniT.J. McCallC. Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain.Obesity (Silver Spring)201220349850410.1038/oby.2011.316 21996662
     [Google Scholar]
  23. ChapoulyC. Tadesse ArgawA. HorngS. CastroK. ZhangJ. AspL. LooH. LaitmanB.M. MarianiJ.N. Straus FarberR. ZaslavskyE. NudelmanG. RaineC.S. JohnG.R. Astrocytic TYMP and VEGFA drive blood–brain barrier opening in inflammatory central nervous system lesions.Brain201513861548156710.1093/brain/awv077 25805644
     [Google Scholar]
  24. BergR.M.G. MøllerK. BaileyD.M. Neuro-oxidative-nitrosative stress in sepsis.J. Cereb. Blood Flow Metab.20113171532154410.1038/jcbfm.2011.48 21487413
     [Google Scholar]
  25. BozzaF.A. D’AvilaJ.C. RitterC. SonnevilleR. SharsharT. Dal-PizzolF. Bioenergetics, mitochondrial dysfunction, and oxidative stress in the pathophysiology of septic encephalopathy.Shock201339Suppl. 1101610.1097/SHK.0b013e31828fade1 23481496
     [Google Scholar]
  26. CalabreseV. MancusoC. CalvaniM. RizzarelliE. ButterfieldD.A. GiuffridaS.A.M. Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity.Nat. Rev. Neurosci.200781076677510.1038/nrn2214 17882254
     [Google Scholar]
  27. CesarP.A.L. Mitochondrial dysfunction during sepsis.Endocr. Metab. Immune Disord. Drug Targets201010321422310.2174/187153010791936946 20509844
     [Google Scholar]
  28. BarichelloT. FortunatoJ.J. VitaliÂ.M. FeierG. ReinkeA. MoreiraJ.C.F. QuevedoJ. Dal-PizzolF. Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation.Crit. Care Med.200634388688910.1097/01.CCM.0000201880.50116.12 16505668
     [Google Scholar]
  29. XieK. ZhangY. WangY. MengX. WangY. YuY. ChenH. Hydrogen attenuates sepsis-associated encephalopathy by NRF2 mediated NLRP3 pathway inactivation.Inflamm. Res.202069769771010.1007/s00011‑020‑01347‑9 32350570
     [Google Scholar]
  30. YuY. FengJ. LianN. YangM. XieK. WangG. WangC. YuY. Hydrogen gas alleviates blood-brain barrier impairment and cognitive dysfunction of septic mice in an Nrf2-dependent pathway.Int. Immunopharmacol.20208510658510.1016/j.intimp.2020.106585 32447221
     [Google Scholar]
  31. CalabreseV. CorneliusC. Dinkova-KostovaA.T. CalabreseE.J. MattsonM.P. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders.Antioxid. Redox Signal.201013111763181110.1089/ars.2009.3074 20446769
     [Google Scholar]
  32. CalabreseV. CorneliusC. Dinkova-KostovaA.T. CalabreseE.J. Vitagenes, cellular stress response, and acetylcarnitine: Relevance to hormesis.Biofactors200935214616010.1002/biof.22 19449442
     [Google Scholar]
  33. WangZ. LiuL. LiuL. Vitamin C as a treatment for organ failure in sepsis.Eur. J. Med. Res.202328122210.1186/s40001‑023‑01183‑7 37408078
     [Google Scholar]
  34. ZhangN. ZhaoW. HuZ.J. GeS.M. HuoY. LiuL.X. GaoB.L. Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats.Sci. Rep.20211111451110.1038/s41598‑021‑93861‑x 34267240
     [Google Scholar]
  35. ParkJ.E. ShinT.G. JoI.J. JeonK. SuhG.Y. ParkM. WonH. ChungC.R. HwangS.Y. Impact of vitamin C and thiamine administration on delirium-free days in patients with septic shock.J. Clin. Med.20209119310.3390/jcm9010193 31936824
     [Google Scholar]
  36. ZhaiQ. LaiD. CuiP. ZhouR. ChenQ. HouJ. SuY. PanL. YeH. ZhaoJ.W. FangX. Selective activation of basal forebrain cholinergic neurons attenuates polymicrobial sepsis-induced inflammation via the cholinergic anti-inflammatory pathway.Crit. Care Med.20174510e1075e108210.1097/CCM.0000000000002646 28806219
     [Google Scholar]
  37. CollingridgeG.L. AbrahamW.C. Glutamate receptors and synaptic plasticity: The impact of evans and watkins.Neuropharmacology202220610892210.1016/j.neuropharm.2021.108922 34919905
     [Google Scholar]
  38. ParkM. AMPA receptor trafficking for postsynaptic potentiation.Front. Cell. Neurosci.20181236110.3389/fncel.2018.00361 30364291
     [Google Scholar]
  39. NicollR.A. SchulmanH. Synaptic memory and CaMKII.Physiol. Rev.202310342897294510.1152/physrev.00034.2022 37290118
     [Google Scholar]
  40. ScheffS.W. PriceD.A. SchmittF.A. DeKoskyS.T. MufsonE.J. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment.Neurology200768181501150810.1212/01.wnl.0000260698.46517.8f 17470753
     [Google Scholar]
  41. VanhauteH. CeccariniJ. MichielsL. KooleM. SunaertS. LemmensR. TriauE. EmsellL. VandenbulckeM. Van LaereK. In vivo synaptic density loss is related to tau deposition in amnestic mild cognitive impairment.Neurology2020955e545e55310.1212/WNL.0000000000009818 32493717
     [Google Scholar]
  42. RobinsonJ.L. Molina-PorcelL. CorradaM.M. RaibleK. LeeE.B. LeeV.M.Y. KawasC.H. TrojanowskiJ.Q. Perforant path synaptic loss correlates with cognitive impairment and Alzheimer’s disease in the oldest-old.Brain201413792578258710.1093/brain/awu190 25012223
     [Google Scholar]
  43. ManabeT. RáczI. SchwartzS. OberleL. SantarelliF. EmmrichJ.V. NeherJ.J. HenekaM.T. Systemic inflammation induced the delayed reduction of excitatory synapses in the CA3 during ageing.J. Neurochem.2021159352554210.1111/jnc.15491 34379806
     [Google Scholar]
  44. SongZ. ShenF. ZhangZ. WuS. ZhuG. Calpain inhibition ameliorates depression-like behaviors by reducing inflammation and promoting synaptic protein expression in the hippocampus.Neuropharmacology202017410817510.1016/j.neuropharm.2020.108175 32492450
     [Google Scholar]
  45. KondoS. KohsakaS. OkabeS. Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo.Mol. Brain2011412710.1186/1756‑6606‑4‑27 21682853
     [Google Scholar]
  46. HosseiniS. WilkE. Michaelsen-PreusseK. GerhauserI. BaumgärtnerW. GeffersR. SchughartK. KorteM. Long-term neuroinflammation induced by influenza a virus infection and the impact on hippocampal neuron morphology and function.J. Neurosci.201838123060308010.1523/JNEUROSCI.1740‑17.2018 29487124
     [Google Scholar]
  47. ZhangJ. MalikA. ChoiH.B. KoR.W.Y. Dissing-OlesenL. MacVicarB.A. Microglial CR3 activation triggers long-term synaptic depression in the hippocampus via NADPH oxidase.Neuron201482119520710.1016/j.neuron.2014.01.043 24631344
     [Google Scholar]
  48. MoraesC.A. SantosG. SpohrT.C.L.S. D’AvilaJ.C. LimaF.R.S. BenjamimC.F. BozzaF.A. GomesF.C.A. Activated microglia-induced deficits in excitatory synapses through IL-1β: implications for cognitive impairment in sepsis.Mol. Neurobiol.201552165366310.1007/s12035‑014‑8868‑5 25257696
     [Google Scholar]
  49. ChungH.Y. WickelJ. HahnN. MeinN. SchwarzbrunnM. KochP. CeangaM. HaselmannH. Baade-BüttnerC. von StackelbergN. HempelN. SchmidlL. GrothM. AndreasN. GötzeJ. ColdeweyS.M. BauerM. MawrinC. DargvainieneJ. LeypoldtF. SteinkeS. WangZ.Q. HustM. GeisC. Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy.Sci. Adv.2023921eabq780610.1126/sciadv.abq7806 37235660
     [Google Scholar]
  50. JiangJ. ZouY. XieC. YangM. TongQ. YuanM. PeiX. DengS. TianM. XiaoL. GongY. Oxytocin alleviates cognitive and memory impairments by decreasing hippocampal microglial activation and synaptic defects via OXTR/ERK/STAT3 pathway in a mouse model of sepsis-associated encephalopathy.Brain Behav. Immun.202311419521310.1016/j.bbi.2023.08.023 37648002
     [Google Scholar]
  51. BluemelP. WickelJ. GrünewaldB. CeangaM. KeinerS. WitteO.W. RedeckerC. GeisC. KunzeA. Sepsis promotes gliogenesis and depletes the pool of radial glia like stem cells in the hippocampus.Exp. Neurol.202133811359110.1016/j.expneurol.2020.113591 33387461
     [Google Scholar]
  52. BeyerM.M.S. LonnemannN. RemusA. LatzE. HenekaM.T. KorteM. Enduring Changes in neuronal function upon systemic inflammation are NLRP3 inflammasome dependent.J. Neurosci.202040285480549410.1523/JNEUROSCI.0200‑20.2020 32499379
     [Google Scholar]
  53. QinZ. ZhouC. XiaoX. GuoC. Metformin attenuates sepsis-induced neuronal injury and cognitive impairment.BMC Neurosci.20212217810.1186/s12868‑021‑00683‑8 34911449
     [Google Scholar]
  54. ZivkovicA.R. SedlaczekO. Von HakenR. SchmidtK. BrennerT. WeigandM.A. BadingH. BengtsonC.P. HoferS. Muscarinic M1 receptors modulate endotoxemia-induced loss of synaptic plasticity.Acta Neuropathol. Commun.201536710.1186/s40478‑015‑0245‑8 26531194
     [Google Scholar]
  55. StachowiczK. Pańczyszyn-TrzewikP. Sowa-KućmaM. MisztakP. Changes in working memory induced by lipopolysaccharide administration in mice are associated with metabotropic glutamate receptors 5 and contrast with changes induced by cyclooxygenase-2: Involvement of postsynaptic density protein 95 and down syndrome cell adhesion molecule.Neuropeptides202310010234710.1016/j.npep.2023.102347 37182274
     [Google Scholar]
  56. YangS. SeoH. WangM. ArnstenA.F.T. NMDAR neurotransmission needed for persistent neuronal firing: Potential roles in mental disorders.Front. Psychiatry20211265432210.3389/fpsyt.2021.654322 33897503
     [Google Scholar]
  57. ZongM. YuanH. HeX. ZhouZ. QiuX. YangJ. JiM. Disruption of striatal-enriched protein tyrosine phosphatase signaling might contribute to memory impairment in a mouse model of sepsis-associated encephalopathy.Neurochem. Res.201944122832284210.1007/s11064‑019‑02905‑2 31691882
     [Google Scholar]
  58. TauberS.C. DjukicM. GossnerJ. EiffertH. BrückW. NauR. Sepsis-associated encephalopathy and septic encephalitis: An update.Expert Rev. Anti Infect. Ther.202119221523110.1080/14787210.2020.1812384 32808580
     [Google Scholar]
  59. TangC. JinY. WangH. The biological alterations of synapse/synapse formation in sepsis-associated encephalopathy.Front. Synaptic Neurosci.202214105460510.3389/fnsyn.2022.1054605 36530954
     [Google Scholar]
  60. Peters van TonA.M. VerbeekM.M. AlkemaW. PickkersP. AbdoW.F. Downregulation of synapse-associated protein expression and loss of homeostatic microglial control in cerebrospinal fluid of infectious patients with delirium and patients with Alzheimer’s disease.Brain Behav. Immun.20208965666710.1016/j.bbi.2020.06.027 32592865
     [Google Scholar]
  61. JiangP.P. PengS.S. PankratovaS. LuoP. ZhouP. ChenY. Proteins involved in synaptic plasticity are downregulated in the cerebrospinal fluid of infants with clinical sepsis complicated by neuroinflammation.Front. Cell. Neurosci.20221688721210.3389/fncel.2022.887212 35634471
     [Google Scholar]
  62. SanchoL. ContrerasM. AllenN.J. Glia as sculptors of synaptic plasticity.Neurosci. Res.2021167172910.1016/j.neures.2020.11.005 33316304
     [Google Scholar]
  63. AndohM. KoyamaR. Microglia regulate synaptic development and plasticity.Dev. Neurobiol.202181556859010.1002/dneu.22814 33583110
     [Google Scholar]
  64. WiltonD.K. Dissing-OlesenL. StevensB. Neuron-glia signaling in synapse elimination.Annu. Rev. Neurosci.201942110712710.1146/annurev‑neuro‑070918‑050306 31283900
     [Google Scholar]
  65. VukojicicA. DelestréeN. FletcherE.V. PagiazitisJ.G. SankaranarayananS. YednockT.A. BarresB.A. MentisG.Z. The classical complement pathway mediates microglia-dependent remodeling of spinal motor circuits during development and in SMA.Cell Rep.2019291030873100.e710.1016/j.celrep.2019.11.013 31801075
     [Google Scholar]
  66. XinY.R. JiangJ.X. HuY. PanJ.P. MiX.N. GaoQ. XiaoF. ZhangW. LuoH.M. The immune system drives synapse loss during Lipopolysaccharide-induced learning and memory impairment in mice.Front. Aging Neurosci.20191127910.3389/fnagi.2019.00279 31803043
     [Google Scholar]
  67. CangalayaC. WegmannS. SunW. DiezL. GottfriedA. RichterK. StoyanovS. PakanJ. FischerK.D. DityatevA. Real-time mechanisms of exacerbated synaptic remodeling by microglia in acute models of systemic inflammation and tauopathy.Brain Behav. Immun.202311024525910.1016/j.bbi.2023.02.023 36906076
     [Google Scholar]
  68. StephanA.H. BarresB.A. StevensB. The complement system: An unexpected role in synaptic pruning during development and disease.Annu. Rev. Neurosci.201235136938910.1146/annurev‑neuro‑061010‑113810 22715882
     [Google Scholar]
  69. VasekM.J. GarberC. DorseyD. DurrantD.M. BollmanB. SoungA. YuJ. Perez-TorresC. FrouinA. WiltonD.K. FunkK. DeMastersB.K. JiangX. BowenJ.R. MennerickS. RobinsonJ.K. GarbowJ.R. TylerK.L. SutharM.S. SchmidtR.E. StevensB. KleinR.S. A complement–microglial axis drives synapse loss during virus-induced memory impairment.Nature2016534760853854310.1038/nature18283 27337340
     [Google Scholar]
  70. Scott-HewittN. PerrucciF. MoriniR. ErreniM. MahoneyM. WitkowskaA. CareyA. FaggianiE. SchuetzL.T. MasonS. TamboriniM. BizzottoM. PassoniL. FilipelloF. JahnR. StevensB. MatteoliM. Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia.EMBO J.20203916e10538010.15252/embj.2020105380 32657463
     [Google Scholar]
  71. FilipelloF. MoriniR. CorradiniI. ZerbiV. CanziA. MichalskiB. ErreniM. MarkicevicM. Starvaggi-CucuzzaC. OteroK. PiccioL. CignarellaF. PerrucciF. TamboriniM. GenuaM. RajendranL. MennaE. VetranoS. FahnestockM. PaolicelliR.C. MatteoliM. The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity.Immunity2018485979991.e810.1016/j.immuni.2018.04.016 29752066
     [Google Scholar]
  72. DanielskiL.G. GiustinaA.D. GoldimM.P. FlorentinoD. MathiasK. GarbossaL. de Bona SchraiberR. LaurentinoA.O.M. GoulartM. MichelsM. de QueirozK.B. KohlhofM. RezinG.T. FortunatoJ.J. QuevedoJ. BarichelloT. Dal-PizzolF. CoimbraR.S. PetronilhoF. Vitamin B6 reduces neurochemical and long-term cognitive alterations after polymicrobial sepsis: Involvement of the kynurenine pathway modulation.Mol. Neurobiol.20185565255526810.1007/s12035‑017‑0706‑0 28879460
     [Google Scholar]
  73. PaïdassiH. Tacnet-DelormeP. GarlattiV. DarnaultC. GhebrehiwetB. GaboriaudC. ArlaudG.J. FrachetP. C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition.J. Immunol.200818042329233810.4049/jimmunol.180.4.2329 18250442
     [Google Scholar]
  74. LiS. LiB. ZhangL. ZhangG. SunJ. JiM. YangJ. A complement-microglial axis driving inhibitory synapse related protein loss might contribute to systemic inflammation-induced cognitive impairment.Int. Immunopharmacol.20208710681410.1016/j.intimp.2020.106814 32707491
     [Google Scholar]
  75. WeinhardL. di BartolomeiG. BolascoG. MachadoP. SchieberN.L. NeniskyteU. ExigaM. VadisiuteA. RaggioliA. SchertelA. SchwabY. GrossC.T. Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction.Nat. Commun.201891122810.1038/s41467‑018‑03566‑5 29581545
     [Google Scholar]
  76. KettenmannH. KirchhoffF. VerkhratskyA. Microglia: new roles for the synaptic stripper.Neuron2013771101810.1016/j.neuron.2012.12.023 23312512
     [Google Scholar]
  77. PradaI. GabrielliM. TurolaE. IorioA. D’ArrigoG. ParolisiR. De LucaM. PacificiM. BastoniM. LombardiM. LegnameG. CojocD. BuffoA. FurlanR. PeruzziF. VerderioC. Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations.Acta Neuropathol.2018135452955010.1007/s00401‑017‑1803‑x 29302779
     [Google Scholar]
  78. MoraesC.A. HottzE.D. Dos Santos OrnellasD. AdesseD. de AzevedoC.T. d’AvilaJ.C. Zaverucha-do-ValleC. Maron-GutierrezT. BarbosaH.S. BozzaP.T. BozzaF.A. Microglial NLRP3 inflammasome induces excitatory synaptic loss through IL-1β-enriched microvesicle release: Implications for sepsis-associated encephalopathy.Mol. Neurobiol.202360248149410.1007/s12035‑022‑03067‑z 36280654
     [Google Scholar]
  79. HanQ. LinQ. HuangP. ChenM. HuX. FuH. HeS. ShenF. ZengH. DengY. Microglia-derived IL-1β contributes to axon development disorders and synaptic deficit through p38-MAPK signal pathway in septic neonatal rats.J. Neuroinflammation20171415210.1186/s12974‑017‑0805‑x 28288671
     [Google Scholar]
  80. ItoH. HosomiS. KoyamaY. MatsumotoH. ImamuraY. OguraH. OdaJ. Sepsis-associated encephalopathy: A mini-review of inflammation in the brain and body.Front. Aging Neurosci.20221491286610.3389/fnagi.2022.912866 35711904
     [Google Scholar]
  81. SheppardO. ColemanM.P. DurrantC.S. Lipopolysaccharide-induced neuroinflammation induces presynaptic disruption through a direct action on brain tissue involving microglia-derived interleukin 1 beta.J. Neuroinflammation201916110610.1186/s12974‑019‑1490‑8 31103036
     [Google Scholar]
  82. LimS.H. ParkE. YouB. JungY. ParkA.R. ParkS.G. LeeJ.R. Neuronal synapse formation induced by microglia and interleukin 10.PLoS One2013811e8121810.1371/journal.pone.0081218 24278397
     [Google Scholar]
  83. RichwineA.F. SparkmanN.L. DilgerR.N. BuchananJ.B. JohnsonR.W. Cognitive deficits in interleukin-10-deficient mice after peripheral injection of lipopolysaccharide.Brain Behav. Immun.200923679480210.1016/j.bbi.2009.02.020 19272439
     [Google Scholar]
  84. Welser-AlvesJ.V. MilnerR. Microglia are the major source of TNF-α and TGF-β1 in postnatal glial cultures; regulation by cytokines, lipopolysaccharide, and vitronectin.Neurochem. Int.2013631475310.1016/j.neuint.2013.04.007 23619393
     [Google Scholar]
  85. ZippF. BittnerS. SchaferD.P. Cytokines as emerging regulators of central nervous system synapses.Immunity202356591492510.1016/j.immuni.2023.04.011 37163992
     [Google Scholar]
  86. MaoY. ZhangA. YangH. ZhangC. Identification of IL-8 in CSF as a potential biomarker in sepsis-associated encephalopathy.Cytokine202317215639010.1016/j.cyto.2023.156390 37812997
     [Google Scholar]
  87. MégarbaneB. MarchalP. Marfaing-KokaA. BelliardO. JacobsF. CharyI. BrivetF.G. Increased diffusion of soluble adhesion molecules in meningitis, severe sepsis and systemic inflammatory response without neurological infection is associated with intrathecal shedding in cases of meningitis.Intensive Care Med.200430586787410.1007/s00134‑004‑2253‑1 15067502
     [Google Scholar]
  88. MomonakaH. HasegawaS. MatsushigeT. InoueH. KajimotoM. OkadaS. NakatsukaK. MorishimaT. IchiyamaT. High mobility group box 1 in patients with 2009 pandemic H1N1 influenza-associated encephalopathy.Brain Dev.201436648448810.1016/j.braindev.2013.07.001 23907181
     [Google Scholar]
  89. Hasegawa-IshiiS. InabaM. ShimadaA. Widespread time-dependent changes in tissue cytokine concentrations in brain regions during the acute phase of endotoxemia in mice.Neurotoxicology202076677410.1016/j.neuro.2019.10.006 31628962
     [Google Scholar]
  90. LynchM.A. Neuroinflammatory changes negatively impact on LTP: A focus on IL-1β.Brain Res.2015162119720410.1016/j.brainres.2014.08.040 25193603
     [Google Scholar]
  91. AvitalA. GoshenI. KamslerA. SegalM. IverfeldtK. Richter-LevinG. YirmiyaR. Impaired interleukin‐1 signaling is associated with deficits in hippocampal memory processes and neural plasticity.Hippocampus200313782683410.1002/hipo.10135 14620878
     [Google Scholar]
  92. WangP. RothwellN.J. PinteauxE. BroughD. Neuronal injury induces the release of pro-interleukin-1β from activated microglia in vitro.Brain Res.200812361710.1016/j.brainres.2008.08.001 18722361
     [Google Scholar]
  93. ImamuraY. WangH. MatsumotoN. MuroyaT. ShimazakiJ. OguraH. ShimazuT. Interleukin-1β causes long-term potentiation deficiency in a mouse model of septic encephalopathy.Neuroscience2011187636910.1016/j.neuroscience.2011.04.063 21571042
     [Google Scholar]
  94. ZhangR. SunL. HayashiY. LiuX. KoyamaS. WuZ. NakanishiH. Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1β.Neurobiol. Dis.2010381687710.1016/j.nbd.2009.12.028 20060906
     [Google Scholar]
  95. MishraA. KimH.J. ShinA.H. ThayerS.A. Synapse loss induced by interleukin-1β requires pre- and post-synaptic mechanisms.J. Neuroimmune Pharmacol.20127357157810.1007/s11481‑012‑9342‑7 22311599
     [Google Scholar]
  96. BellingacciL. CanonichesiJ. ManciniA. ParnettiL. Di FilippoM. Cytokines, synaptic plasticity and network dynamics: A matter of balance.Neural Regen. Res.202318122569257210.4103/1673‑5374.371344 37449591
     [Google Scholar]
  97. SerantesR. ArnalichF. FigueroaM. SalinasM. Andrés-MateosE. CodoceoR. RenartJ. MatuteC. CavadaC. CuadradoA. MontielC. Interleukin-1β enhances GABAA receptor cell-surface expression by a phosphatidylinositol 3-kinase/Akt pathway: Relevance to sepsis-associated encephalopathy.J. Biol. Chem.200628121146321464310.1074/jbc.M512489200 16567807
     [Google Scholar]
  98. WangD.S. ZurekA.A. LeckerI. YuJ. AbramianA.M. AvramescuS. DaviesP.A. MossS.J. LuW.Y. OrserB.A. Memory deficits induced by inflammation are regulated by α5-subunit-containing GABAA receptors.Cell Rep.20122348849610.1016/j.celrep.2012.08.022 22999935
     [Google Scholar]
  99. MurdacaG. PaladinF. CasciaroM. VicarioC.M. GangemiS. MartinoG. Neuro-inflammaging and psychopathological distress.Biomedicines2022109213310.3390/biomedicines10092133 36140234
     [Google Scholar]
  100. TangD. KangR. ZehH.J. LotzeM.T. The multifunctional protein HMGB1: 50 years of discovery.Nat. Rev. Immunol.2023231282484110.1038/s41577‑023‑00894‑6 37322174
     [Google Scholar]
  101. Sundén-CullbergJ. Norrby-TeglundA. RouhiainenA. RauvalaH. HermanG. TraceyK.J. LeeM.L. AnderssonJ. TokicsL. TreutigerC.J. Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock.Crit. Care Med.200533356457310.1097/01.CCM.0000155991.88802.4D 15753748
     [Google Scholar]
  102. FrankM.G. WeberM.D. WatkinsL.R. MaierS.F. Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming.Brain Behav. Immun.2015481710.1016/j.bbi.2015.03.010 25816800
     [Google Scholar]
  103. FranklinT.C. WohlebE.S. ZhangY. FogaçaM. HareB. DumanR.S. Persistent increase in microglial RAGE contributes to chronic stress-induced priming of depressive-like behavior.Biol. Psychiatry2018831506010.1016/j.biopsych.2017.06.034 28882317
     [Google Scholar]
  104. WangB. HuangX. PanX. ZhangT. HouC. SuW.J. LiuL.L. LiJ.M. WangY.X. Minocycline prevents the depressive-like behavior through inhibiting the release of HMGB1 from microglia and neurons.Brain Behav. Immun.20208813214310.1016/j.bbi.2020.06.019 32553784
     [Google Scholar]
  105. XiongY. YangJ. TongH. ZhuC. PangY. HMGB1 augments cognitive impairment in sepsis‐associated encephalopathy by binding to MD‐2 and promoting NLRP3 ‐induced neuroinflammation.Psychogeriatrics202222216717910.1111/psyg.12794 34931753
     [Google Scholar]
  106. XinY. WangJ. ChuT. ZhouY. LiuC. XuA. Electroacupuncture alleviates neuroinflammation by inhibiting the HMGB1 signaling pathway in rats with sepsis-associated encephalopathy.Brain Sci.20221212173210.3390/brainsci12121732 36552192
     [Google Scholar]
  107. Valdés-FerrerS.I. Rosas-BallinaM. OlofssonP.S. LuB. DanchoM.E. LiJ. YangH. PavlovV.A. ChavanS.S. TraceyK.J. High-mobility group box 1 mediates persistent splenocyte priming in sepsis survivors: Evidence from a murine model.Shock201340649249510.1097/SHK.0000000000000050 24089009
     [Google Scholar]
  108. YinX.Y. TangX.H. WangS.X. ZhaoY.C. JiaM. YangJ.J. JiM.H. ShenJ.C. HMGB1 mediates synaptic loss and cognitive impairment in an animal model of sepsis-associated encephalopathy.J. Neuroinflammation20232016910.1186/s12974‑023‑02756‑3 36906561
     [Google Scholar]
  109. ChavanS.S. HuertaP.T. RobbiatiS. Valdes-FerrerS.I. OchaniM. DanchoM. FrankfurtM. VolpeB.T. TraceyK.J. DiamondB. HMGB1 mediates cognitive impairment in sepsis survivors.Mol. Med.201218693093710.2119/molmed.2012.00195 22634723
     [Google Scholar]
  110. Dal-PizzolF. PasqualiM. QuevedoJ. GelainD.P. MoreiraJ.C.F. Is there a role for high mobility group box 1 and the receptor for advanced glycation end products in the genesis of long-term cognitive impairment in sepsis survivors?Mol. Med.201218101357135810.2119/molmed.2012.00317 23114886
     [Google Scholar]
  111. MatsumotoH. MatsumotoN. OguraH. ShimazakiJ. YamakawaK. YamamotoK. ShimazuT. The clinical significance of circulating soluble RAGE in patients with severe sepsis.J. Trauma Acute Care Surg.20157861086109410.1097/TA.0000000000000651 26002402
     [Google Scholar]
  112. Nogueira-MachadoJ.A. de Oliveira VolpeC.M. HMGB-1 as a target for inflammation controlling.Recent Pat. Endocr. Metab. Immune Drug Discov.20126320120910.2174/187221412802481784 22845335
     [Google Scholar]
  113. WangH. TangY. FanZ. LvB. XiaoX. ChenF. High-mobility group box 1 protein induces tissue factor expression in vascular endothelial cells via activation of NF-κB and Egr-1.Thromb. Haemost.2009102835235910.1160/TH08‑11‑0759 19652887
     [Google Scholar]
  114. GasparottoJ. GirardiC.S. SomensiN. RibeiroC.T. MoreiraJ.C.F. MichelsM. SonaiB. RochaM. SteckertA.V. BarichelloT. QuevedoJ. Dal-PizzolF. GelainD.P. Receptor for advanced glycation end products mediates sepsis-triggered amyloid-β accumulation, Tau phosphorylation, and cognitive impairment.J. Biol. Chem.2018293122624410.1074/jbc.M117.786756 29127203
     [Google Scholar]
  115. ShiJ. XuH. CavagnaroM.J. LiX. FangJ. Blocking HMGB1/RAGE signaling by berberine alleviates A1 astrocyte and attenuates sepsis-associated encephalopathy.Front. Pharmacol.20211276018610.3389/fphar.2021.760186 34867376
     [Google Scholar]
  116. TurrigianoG.G. LeslieK.R. DesaiN.S. RutherfordL.C. NelsonS.B. Activity-dependent scaling of quantal amplitude in neocortical neurons.Nature1998391667089289610.1038/36103 9495341
     [Google Scholar]
  117. RizzoF.R. MusellaA. De VitoF. FresegnaD. BullittaS. VanniV. GuadalupiL. Stampanoni BassiM. ButtariF. MandolesiG. CentonzeD. GentileA. Tumor necrosis factor and interleukin-1 β modulate synaptic plasticity during Neuroinflammation.Neural Plast.2018201811210.1155/2018/8430123 29861718
     [Google Scholar]
  118. CalsavaraA.C. SorianiF.M. VieiraL.Q. CostaP.A. RachidM.A. TeixieraA.L. TNFR1 absence protects against memory deficit induced by sepsis possibly through over-expression of hippocampal BDNF.Metab. Brain Dis.201530366967810.1007/s11011‑014‑9610‑8 25148914
     [Google Scholar]
  119. TianL. StefanidakisM. NingL. Van LintP. Nyman-HuttunenH. LibertC. ItoharaS. MishinaM. RauvalaH. GahmbergC.G. Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage.J. Cell Biol.2007178468770010.1083/jcb.200612097 17682049
     [Google Scholar]
  120. PaetauS. RolovaT. NingL. GahmbergC.G. Neuronal ICAM-5 inhibits microglia adhesion and phagocytosis and promotes an anti-inflammatory response in LPS stimulated microglia.Front. Mol. Neurosci.20171043110.3389/fnmol.2017.00431 29311819
     [Google Scholar]
  121. GahmbergC.G. NingL. PaetauS. ICAM-5: A neuronal dendritic adhesion molecule involved in immune and neuronal functions.Adv. Neurobiol.2014811713210.1007/978‑1‑4614‑8090‑7_6 25300135
     [Google Scholar]
  122. GyonevaS. TraynelisS.F. Norepinephrine modulates the motility of resting and activated microglia via different adrenergic receptors.J. Biol. Chem.201328821152911530210.1074/jbc.M113.458901 23548902
     [Google Scholar]
  123. StowellR.D. SipeG.O. DawesR.P. BatchelorH.N. LordyK.A. WhitelawB.S. StoesselM.B. BidlackJ.M. BrownE. SurM. MajewskaA.K. Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex.Nat. Neurosci.201922111782179210.1038/s41593‑019‑0514‑0 31636451
     [Google Scholar]
  124. ZongM.M. ZhouZ.Q. JiM.H. JiaM. TangH. YangJ.J. Activation of β2-adrenoceptor attenuates sepsis-induced hippocampus-dependent cognitive impairments by reversing neuroinflammation and synaptic abnormalities.Front. Cell. Neurosci.20191329310.3389/fncel.2019.00293 31354429
     [Google Scholar]
  125. XuX. LiuL. WangY. WangC. ZhengQ. LiuQ. LiZ. BaiX. LiuX. Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis.Brain Behav. Immun.20198085987010.1016/j.bbi.2019.05.038 31145977
     [Google Scholar]
  126. Garrido-MesaN. ZarzueloA. GálvezJ. Minocycline: far beyond an antibiotic.Br. J. Pharmacol.2013169233735210.1111/bph.12139 23441623
     [Google Scholar]
  127. MichelsM. VieiraA.S. VuoloF. ZapeliniH.G. MendonçaB. MinaF. DominguiniD. SteckertA. SchuckP.F. QuevedoJ. PetronilhoF. Dal-PizzolF. The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.Brain Behav. Immun.201543545910.1016/j.bbi.2014.07.002 25019583
     [Google Scholar]
  128. HoshinoK. HayakawaM. MorimotoY. Minocycline prevents the impairment of hippocampal long-term potentiation in the septic mouse.Shock201748220921410.1097/SHK.0000000000000847 28187038
     [Google Scholar]
  129. HenryC.J. HuangY. WynneA. HankeM. HimlerJ. BaileyM.T. SheridanJ.F. GodboutJ.P. Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia.J. Neuroinflammation2008511510.1186/1742‑2094‑5‑15 18477398
     [Google Scholar]
  130. Tomás-CamardielM. RiteI. HerreraA.J. de PablosR.M. CanoJ. MachadoA. VeneroJ.L. Minocycline reduces the lipopolysaccharide-induced inflammatory reaction, peroxynitrite-mediated nitration of proteins, disruption of the blood–brain barrier, and damage in the nigral dopaminergic system.Neurobiol. Dis.200416119020110.1016/j.nbd.2004.01.010 15207276
     [Google Scholar]
  131. LiuY. ZhangY. ZhengX. FangT. YangX. LuoX. GuoA. NewellK.A. HuangX.F. YuY. Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice.J. Neuroinflammation201815111210.1186/s12974‑018‑1141‑5 29669582
     [Google Scholar]
  132. WuX. LiuC. ChenL. DuY.F. HuM. ReedM.N. LongY. SuppiramaniamV. HongH. TangS.S. Protective effects of tauroursodeoxycholic acid on lipopolysaccharide-induced cognitive impairment and neurotoxicity in mice.Int. Immunopharmacol.20197216617510.1016/j.intimp.2019.03.065 30986644
     [Google Scholar]
  133. ImH. JuI.G. KimJ.H. LeeS. OhM.S. Trichosanthis semen and zingiberis rhizoma mixture ameliorates lipopolysaccharide-induced memory dysfunction by inhibiting neuroinflammation.Int. J. Mol. Sci.202223221401510.3390/ijms232214015 36430493
     [Google Scholar]
  134. van PraagH. KempermannG. GageF.H. Neural consequences of enviromental enrichment.Nat. Rev. Neurosci.20001319119810.1038/35044558 11257907
     [Google Scholar]
  135. WuX. JiM. YinX. GuH. ZhuT. WangR. YangJ. ShenJ. Reduced inhibition underlies early life LPS exposure induced-cognitive impairment: Prevention by environmental enrichment.Int. Immunopharmacol.202210810872410.1016/j.intimp.2022.108724 35378446
     [Google Scholar]
  136. JiM.H. TangH. LuoD. QiuL.L. JiaM. YuanH.M. FengS.W. YangJ.J. Environmental conditions differentially affect neurobehavioral outcomes in a mouse model of sepsis-associated encephalopathy.Oncotarget2017847823768238910.18632/oncotarget.19595 29137271
     [Google Scholar]
  137. JiangS. WangY.Q. TangY. LuX. GuoD. Environmental enrichment protects against sepsis-associated encephalopathy-induced learning and memory deficits by enhancing the synthesis and release of vasopressin in the supraoptic nucleus.J. Inflamm. Res.20221536337910.2147/JIR.S345108 35079222
     [Google Scholar]
  138. KorneevK.V. Mouse models of sepsis and septic shock.Mol. Biol.201953570471710.1134/S0026893319050108 31661479
     [Google Scholar]
  139. QinM. GaoY. GuoS. LuX. ZhaoQ. GeZ. ZhuH. LiY. Establishment and evaluation of animal models of sepsis-associated encephalopathy.World J. Emerg. Med.202314534935310.5847/wjem.j.1920‑8642.2023.088 37908801
     [Google Scholar]
  140. DejagerL. PinheiroI. DejonckheereE. LibertC. Cecal ligation and puncture: the gold standard model for polymicrobial sepsis?Trends Microbiol.201119419820810.1016/j.tim.2011.01.001 21296575
     [Google Scholar]
  141. SaviF.F. de OliveiraA. de MedeirosG.F. BozzaF.A. MichelsM. SharsharT. Dal-PizzolF. RitterC. What animal models can tell us about long-term cognitive dysfunction following sepsis: A systematic review.Neurosci. Biobehav. Rev.202112438640410.1016/j.neubiorev.2020.12.005 33309906
     [Google Scholar]
  142. GranjaM.G. AlvesL.P. Leardini-TristãoM. SaulM.E. BortoniL.C. de MoraesF.M. FerreiraE.C. de MoraesB.P.T. da SilvaV.Z. dos SantosA.F.R. SilvaA.R. Gonçalves-de-AlbuquerqueC.F. Bambini-JuniorV. WeyrichA.S. RondinaM.T. ZimmermanG.A. de Castro-Faria-NetoH.C. Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life.J. Neuroinflammation20211816010.1186/s12974‑021‑02106‑1 33632243
     [Google Scholar]
  143. LinL. ChenX. ZhouQ. HuangP. JiangS. WangH. DengY. Synaptic structure and alterations in the hippocampus in neonatal rats exposed to lipopolysaccharide.Neurosci. Lett.201970913436410.1016/j.neulet.2019.134364 31288048
     [Google Scholar]
  144. ZhangS. WangX. AiS. OuyangW. LeY. TongJ. Sepsis-induced selective loss of NMDA receptors modulates hippocampal neuropathology in surviving septic mice.PLoS One20171211e018827310.1371/journal.pone.0188273 29176858
     [Google Scholar]
  145. WeberpalsM. HermesM. HermannS. KummerM.P. TerwelD. SemmlerA. BergerM. SchäfersM. HenekaM.T. NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits.J. Neurosci.20092945141771418410.1523/JNEUROSCI.3238‑09.2009 19906966
     [Google Scholar]
  146. VivianiB. BartesaghiS. GardoniF. VezzaniA. BehrensM.M. BartfaiT. BinagliaM. CorsiniE. Di LucaM. GalliC.L. MarinovichM. Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases.J. Neurosci.200323258692870010.1523/JNEUROSCI.23‑25‑08692.2003 14507968
     [Google Scholar]
  147. SpulberS. MateosL. OpricaM. Cedazo-MinguezA. BartfaiT. WinbladB. SchultzbergM. Impaired long term memory consolidation in transgenic mice overexpressing the human soluble form of IL-1ra in the brain.J. Neuroimmunol.20092081-2465310.1016/j.jneuroim.2009.01.010 19211154
     [Google Scholar]
  148. YasumuraM. YoshidaT. YamazakiM. AbeM. NatsumeR. KannoK. UemuraT. TakaoK. SakimuraK. KikusuiT. MiyakawaT. MishinaM. IL1RAPL1 knockout mice show spine density decrease, learning deficiency, hyperactivity and reduced anxiety-like behaviours.Sci. Rep.201441661310.1038/srep06613 25312502
     [Google Scholar]
  149. RossiS. MottaC. MusellaA. CentonzeD. The interplay between inflammatory cytokines and the endocannabinoid system in the regulation of synaptic transmission.Neuropharmacology201596Pt A10511210.1016/j.neuropharm.2014.09.02225268960
     [Google Scholar]
  150. ZhouQ. LinL. LiH. LiY. LiuN. WangH. JiangS. LiQ. ChenZ. LinY. JinH. DengY. Intrahippocampal injection of IL‐1β upregulates Siah1‐mediated degradation of synaptophysin by activation of the ERK signaling in male rat.J. Neurosci. Res.2023101693095110.1002/jnr.25170 36720002
     [Google Scholar]
  151. VezzaniA. VivianiB. Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability.Neuropharmacology201596Pt A708210.1016/j.neuropharm.2014.10.02725445483
     [Google Scholar]
  152. Hisaoka-NakashimaK. OhataK. YoshimotoN. TokudaS. YoshiiN. NakamuraY. WangD. LiuK. WakeH. YoshidaT. AgoY. HashimotoK. NishiboriM. MoriokaN. High-mobility group box 1-mediated hippocampal microglial activation induces cognitive impairment in mice with neuropathic pain.Exp. Neurol.202235511414610.1016/j.expneurol.2022.114146 35738416
     [Google Scholar]
/content/journals/cn/10.2174/1570159X23666241028105746
Loading
The Biological Changes of Synaptic Plasticity in the Pathological Process of Sepsis-associated Encephalopathy
Curr. Neuropharmacol. 23, 359 (2025); https://doi.org/10.2174/1570159X23666241028105746
/content/journals/cn/10.2174/1570159X23666241028105746
/content/journals/cn/10.2174/1570159X23666241028105746
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): inflammatory factors; microglia; neuroinflammation; Sepsis; sepsis-associated encephalopathy; synaptic plasticity

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