Skip to main content

Advertisement

SpringerLink
Log in

Investigating the Potential Mechanisms and Therapeutic Targets of Inflammatory Cytokines in Post-stroke Depression

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Post-stroke depression (PSD) affects approximately one-third of stroke survivors, severely impacting general recovery and quality of life. Despite extensive studies, the exact mechanisms underlying PSD remain elusive. However, emerging evidence implicates proinflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-alpha, and interleukin-18, play critical roles in PSD development. These cytokines contribute to PSD through various mechanisms, including hypothalamic–pituitary–adrenal (HPA) axis dysfunction, neurotransmitter alterations, neurotrophic factor changes, gut microbiota imbalances, and genetic predispositions. This review is aimed at exploring the role of cytokines in stroke and PSD while identifying their potential as specific therapeutic targets for managing PSD. A more profound understanding of the mechanisms regulating inflammatory cytokine expression and anti-inflammatory cytokines like interleukin-10 in PSD may facilitate the development of innovative interventions to improve outcomes for stroke survivors experiencing depression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data Availability

Not applicable.

References

  1. Hackett ML, Pickles K (2014) Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies. Int J Stroke 9(8):1017–1025. https://doi.org/10.1111/ijs.12357

    Article  PubMed  Google Scholar 

  2. Paolucci S, Gandolfo C, Provinciali L, Torta R, Toso V (2006) The Italian multicenter observational study on post-stroke depression (DESTRO). J Neurol 253(5):556–562. https://doi.org/10.1007/s00415-006-0058-6

    Article  PubMed  Google Scholar 

  3. Sharma GS, Gupta A, Khanna M, Prakash NB (2021) Post-stroke depression and its effect on functional outcomes during inpatient rehabilitation. J Neurosci Rural Pract 12(3):543–549. https://doi.org/10.1055/s-0041-1731958

    Article  PubMed  PubMed Central  Google Scholar 

  4. Poynter B, Shuman M, Diaz-Granados N, Kapral M, Grace SL, Stewart DE (2009) Sex differences in the prevalence of post-stroke depression: a systematic review. Psychosomatics 50(6):563–569. https://doi.org/10.1176/appi.psy.50.6.563

    Article  PubMed  Google Scholar 

  5. Sarkar A, Sarmah D, Datta A, Kaur H, Jagtap P, Raut S, Shah B, Singh U, et al (2021) Post-stroke depression: chaos to exposition. Brain Res Bull 168:74–88. https://doi.org/10.1016/j.brainresbull.2020.12.012

    Article  CAS  PubMed  Google Scholar 

  6. Guo J, Wang J, Sun W, Liu X (2022) The advances of post-stroke depression: 2021 update. J Neurol 269(3):1236–1249. https://doi.org/10.1007/s00415-021-10597-4

    Article  PubMed  Google Scholar 

  7. Shi K, Tian DC, Li ZG, Ducruet AF, Lawton MT, Shi FD (2019) Global brain inflammation in stroke. Lancet Neurol 18(11):1058–1066. https://doi.org/10.1016/s1474-4422(19)30078-x

    Article  PubMed  Google Scholar 

  8. Kim JM, Kang HJ, Kim JW, Bae KY, Kim SW, Kim JT, Park MS, Cho KH (2017) Associations of tumor necrosis factor-α and interleukin-1β levels and polymorphisms with post-stroke depression. Am J Geriatr Psychiatry 25(12):1300–1308. https://doi.org/10.1016/j.jagp.2017.07.012

    Article  PubMed  Google Scholar 

  9. Chen Y, Pu J, Liu Y, Tian L, Chen X, Gui S, Xu S, Song X, et al (2020) Pro-inflammatory cytokines are associated with the development of post-stroke depression in the acute stage of stroke: a meta-analysis. Top Stroke Rehabil 27(8):620–629. https://doi.org/10.1080/10749357.2020.1755813

    Article  PubMed  Google Scholar 

  10. Yang L, Zhang Z, Sun D, Xu Z, Zhang X, Li L (2010) The serum interleukin-18 is a potential marker for development of post-stroke depression. Neurol Res 32(4):340–346. https://doi.org/10.1179/016164110x12656393665080

    Article  CAS  PubMed  Google Scholar 

  11. Su JA, Chou SY, Tsai CS, Hung TH (2012) Cytokine changes in the pathophysiology of poststroke depression. Gen Hosp Psychiatry 34(1):35–39. https://doi.org/10.1016/j.genhosppsych.2011.09.020

    Article  PubMed  Google Scholar 

  12. Meng G, Ma X, Li L, Tan Y, Liu X, Liu X, Zhao Y (2017) Predictors of early-onset post-ischemic stroke depression: a cross-sectional study. BMC Neurol 17(1):199. https://doi.org/10.1186/s12883-017-0980-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li Z, Xu H, Xu Y, Lu G, Peng Q, Chen J, Bi R, Li J, et al (2021) Morinda officinalis oligosaccharides alleviate depressive-like behaviors in post-stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation. CNS Neurosci Ther 27(12):1570–1586. https://doi.org/10.1111/cns.13732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yi X, Zhu X, Zhou Y, Zhang D, Li M, Zhu Y, Guo X (2021) The combination of insulin resistance and serum interleukin-1β correlates with post-stroke depression in patients with acute ischemic stroke. Neuropsychiatr Dis Treat 17:735–746. https://doi.org/10.2147/ndt.S291164

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kang HJ, Bae KY, Kim SW, Kim JT, Park MS, Cho KH, Kim JM (2016) Effects of interleukin-6, interleukin-18, and statin use, evaluated at acute stroke, on post-stroke depression during 1-year follow-up. Psychoneuroendocrinology 72:156–160. https://doi.org/10.1016/j.psyneuen.2016.07.001

    Article  CAS  PubMed  Google Scholar 

  16. Korostynski M, Hoinkis D, Piechota M, Golda S, Pera J, Slowik A, Dziedzic T (2021) Toll-like receptor 4-mediated cytokine synthesis and post-stroke depressive symptoms. Transl Psychiatry 11(1):246. https://doi.org/10.1038/s41398-021-01359-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chi CH, Huang YY, Ye SZ, Shao MM, Jiang MX, Yang MY, Wu Q, Shao B, et al (2021) Interleukin-10 level is associated with post-stroke depression in acute ischaemic stroke patients. J Affect Disord 293:254–260. https://doi.org/10.1016/j.jad.2021.06.037

    Article  CAS  PubMed  Google Scholar 

  18. Kim JM, Stewart R, Kim SW, Shin IS, Kim JT, Park MS, Park SW, Kim YH, et al (2012) Associations of cytokine gene polymorphisms with post-stroke depression. World J Biol Psychiatry 13(8):579–587. https://doi.org/10.3109/15622975.2011.588247

    Article  PubMed  Google Scholar 

  19. Wu D, Zhang G, Zhao C, Yang Y, Miao Z, Xu X (2020) Interleukin-18 from neurons and microglia mediates depressive behaviors in mice with post-stroke depression. Brain Behav Immun 88:411–420. https://doi.org/10.1016/j.bbi.2020.04.004

    Article  CAS  PubMed  Google Scholar 

  20. Bossù P, Salani F, Cacciari C, Picchetto L, Cao M, Bizzoni F, Rasura M, Caltagirone C, et al (2009) Disease outcome, alexithymia and depression are differently associated with serum IL-18 levels in acute stroke. Curr Neurovasc Res 6(3):163–170. https://doi.org/10.2174/156720209788970036

    Article  PubMed  Google Scholar 

  21. Turnbull AV, Rivier CL (1999) Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79(1):1–71. https://doi.org/10.1152/physrev.1999.79.1.1

    Article  CAS  PubMed  Google Scholar 

  22. El Husseini N, Laskowitz DT (2014) The role of neuroendocrine pathways in prognosis after stroke. Expert Rev Neurother 14(2):217–232. https://doi.org/10.1586/14737175.2014.877841

    Article  CAS  PubMed  Google Scholar 

  23. Stoll G, Jander S, Schroeter M (1998) Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56(2):149–171. https://doi.org/10.1016/s0301-0082(98)00034-3

    Article  CAS  PubMed  Google Scholar 

  24. Nagy EE, Frigy A, Szász JA, Horváth E (2020) Neuroinflammation and microglia/macrophage phenotype modulate the molecular background of post-stroke depression: a literature review. Exp Ther Med 20(3):2510–2523. https://doi.org/10.3892/etm.2020.8933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zahrai A, Vahid-Ansari F, Daigle M, Albert PR (2020) Fluoxetine-induced recovery of serotonin and norepinephrine projections in a mouse model of post-stroke depression. Transl Psychiatry 10(1):334. https://doi.org/10.1038/s41398-020-01008-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Makhija K, Karunakaran S (2013) The role of inflammatory cytokines on the aetiopathogenesis of depression. Aust N Z J Psychiatry 47(9):828–839. https://doi.org/10.1177/0004867413488220

    Article  PubMed  Google Scholar 

  27. Qiu X, Wang H, Lan Y, Miao J, Pan C, Sun W, Li G, Wang Y, et al (2022) Blood biomarkers of post-stroke depression after minor stroke at three months in males and females. BMC Psychiatry 22(1):162. https://doi.org/10.1186/s12888-022-03805-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kang Y, Yang Y, Wang J, Ma Y, Cheng H, Wan D (2021) Correlation between intestinal flora and serum inflammatory factors in post-stroke depression in ischemic stroke. J Coll Physicians Surg Pak 31(10):1224–1227. https://doi.org/10.29271/jcpsp.2021.10.1224

    Article  PubMed  Google Scholar 

  29. Himmerich H, Patsalos O, Lichtblau N, Ibrahim MAA, Dalton B (2019) Cytokine research in depression: principles, challenges, and open questions. Front Psychiatry 10:30. https://doi.org/10.3389/fpsyt.2019.00030

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wijeratne T, Sales C (2021) Understanding why post-stroke depression may be the norm rather than the exception: the anatomical and neuroinflammatory correlates of post-stroke depression. J Clin Med 10(8). https://doi.org/10.3390/jcm10081674

  31. Chen GY, Nuñez G (2010) Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol 10(12):826–837. https://doi.org/10.1038/nri2873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gülke E, Gelderblom M, Magnus T (2018) Danger signals in stroke and their role on microglia activation after ischemia. Ther Adv Neurol Disord 11:1756286418774254. https://doi.org/10.1177/1756286418774254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chamorro Á, Dirnagl U, Urra X, Planas AM (2016) Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol 15(8):869–881. https://doi.org/10.1016/s1474-4422(16)00114-9

    Article  CAS  PubMed  Google Scholar 

  34. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT (2012) PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev 249(1):158–175. https://doi.org/10.1111/j.1600-065X.2012.01146.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chung HY, Kim DH, Lee EK, Chung KW, Chung S, Lee B, Seo AY, Chung JH, et al (2019) Redefining chronic inflammation in aging and age-related diseases: proposal of the senoinflammation concept. Aging Dis 10(2):367–382. https://doi.org/10.14336/ad.2018.0324

    Article  PubMed  PubMed Central  Google Scholar 

  36. Richard SA, Sackey M, Su Z, Xu H (2017) Pivotal neuroinflammatory and therapeutic role of high mobility group box 1 in ischemic stroke. Biosci Rep 37(6). https://doi.org/10.1042/bsr20171104

  37. Iadecola C, Anrather J (2011) The immunology of stroke: from mechanisms to translation. Nat Med 17(7):796–808. https://doi.org/10.1038/nm.2399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu T, Zhang L, Joo D, Sun SC (2017) NF-κB signaling in inflammation. Signal Transduct Target Ther 2:17023-. https://doi.org/10.1038/sigtrans.2017.23

  39. Pawluk H, Woźniak A, Grześk G, Kołodziejska R, Kozakiewicz M, Kopkowska E, Grzechowiak E, Kozera G (2020) The role of selected pro-inflammatory cytokines in pathogenesis of ischemic stroke. Clin Interv Aging 15:469–484. https://doi.org/10.2147/cia.S233909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cherry JD, Olschowka JA, O’Banion MK (2014) Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflammation 11:98. https://doi.org/10.1186/1742-2094-11-98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mizuma A, Yenari MA (2017) Anti-inflammatory targets for the treatment of reperfusion injury in stroke. Front Neurol 8:467. https://doi.org/10.3389/fneur.2017.00467

    Article  PubMed  PubMed Central  Google Scholar 

  42. Maida CD, Norrito RL, Daidone M, Tuttolomondo A, Pinto A (2020) Neuroinflammatory mechanisms in ischemic stroke: focus on cardioembolic stroke, background, and therapeutic approaches. Int J Mol Sci 21(18). https://doi.org/10.3390/ijms21186454

  43. Gough P, Myles IA (2020) Tumor necrosis factor receptors: pleiotropic signaling complexes and their differential effects. Front Immunol 11:585880. https://doi.org/10.3389/fimmu.2020.585880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ortí-Casañ N, Wu Y, Naudé PJW, De Deyn PP, Zuhorn IS, Eisel ULM (2019) Targeting TNFR2 as a novel therapeutic strategy for Alzheimer’s disease. Front Neurosci 13:49. https://doi.org/10.3389/fnins.2019.00049

    Article  PubMed  PubMed Central  Google Scholar 

  45. Heir R, Stellwagen D (2020) TNF-mediated homeostatic synaptic plasticity: from in vitro to in vivo models. Front Cell Neurosci 14:565841. https://doi.org/10.3389/fncel.2020.565841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zaremba J, Losy J (2001) Early TNF-alpha levels correlate with ischaemic stroke severity. Acta Neurol Scand 104(5):288–295. https://doi.org/10.1034/j.1600-0404.2001.00053.x

    Article  CAS  PubMed  Google Scholar 

  47. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28(6):1233–1244. https://doi.org/10.1161/01.str.28.6.1233

    Article  CAS  PubMed  Google Scholar 

  48. Lambertsen KL, Gregersen R, Meldgaard M, Clausen BH, Heibøl EK, Ladeby R, Knudsen J, Frandsen A, et al (2004) A role for interferon-gamma in focal cerebral ischemia in mice. J Neuropathol Exp Neurol 63(9):942–955. https://doi.org/10.1093/jnen/63.9.942

    Article  CAS  PubMed  Google Scholar 

  49. Yilmaz G, Arumugam TV, Stokes KY, Granger DN (2006) Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 113(17):2105–2112. https://doi.org/10.1161/circulationaha.105.593046

    Article  PubMed  Google Scholar 

  50. Barger SW, Hörster D, Furukawa K, Goodman Y, Krieglstein J, Mattson MP (1995) Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc Natl Acad Sci U S A 92(20):9328–9332. https://doi.org/10.1073/pnas.92.20.9328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chen AQ, Fang Z, Chen XL, Yang S, Zhou YF, Mao L, Xia YP, Jin HJ, et al (2019) Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke. Cell Death Dis 10(7):487. https://doi.org/10.1038/s41419-019-1716-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bonetti NR, Diaz-Cañestro C, Liberale L, Crucet M, Akhmedov A, Merlini M, Reiner MF, Gobbato S, et al (2019) Tumour necrosis factor-α inhibition improves stroke outcome in a mouse model of rheumatoid arthritis. Sci Rep 9(1):2173. https://doi.org/10.1038/s41598-019-38670-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lambertsen KL, Biber K, Finsen B (2012) Inflammatory cytokines in experimental and human stroke. J Cereb Blood Flow Metab 32(9):1677–1698. https://doi.org/10.1038/jcbfm.2012.88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mao L, Wu DH, Hu GH, Fan JH (2023) TLR4 enhances cerebral ischemia/reperfusion injury via regulating NLRP3 inflammasome and autophagy. Mediators Inflamm 2023:9335166. https://doi.org/10.1155/2023/9335166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lasek-Bal A, Jedrzejowska-Szypulka H, Student S, Warsz-Wianecka A, Zareba K, Puz P, Bal W, Pawletko K, et al (2019) The importance of selected markers of inflammation and blood-brain barrier damage for short-term ischemic stroke prognosis. J Physiol Pharmacol 70(2). https://doi.org/10.26402/jpp.2019.2.04

  56. Manolescu BN, Berteanu M, Dumitru L, Dinu H, Iliescu A, Fărcăşanu IC, Oprea E, Vlădoiu S, et al (2011) Dynamics of inflammatory markers in post-acute stroke patients undergoing rehabilitation. Inflammation 34(6):551–558. https://doi.org/10.1007/s10753-010-9262-8

    Article  CAS  PubMed  Google Scholar 

  57. Huţanu A, Iancu M, Bălaşa R, Maier S, Dobreanu M (2018) Predicting functional outcome of ischemic stroke patients in Romania based on plasma CRP, sTNFR-1, D-Dimers, NGAL and NSE measured using a biochip array. Acta Pharmacol Sin 39(7):1228–1236. https://doi.org/10.1038/aps.2018.26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rosa Neto JC, Lira FS, Roy S, Festuccia W (2017) Immunometabolism: molecular mechanisms, diseases, and therapies 2016. Mediators Inflamm 2017:8230298. https://doi.org/10.1155/2017/8230298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Svensson EH, Söderholm M, Abul-Kasim K, Engström G (2017) Tumor necrosis factor receptor 1 and 2 are associated with risk of intracerebral hemorrhage. Stroke 48(10):2710–2715. https://doi.org/10.1161/strokeaha.117.017849

    Article  CAS  PubMed  Google Scholar 

  60. Hansen RB, Laursen CCH, Nawaz N, Madsen JS, Nielsen HH, Kruuse C, Møller A, Degn M, et al (2021) Leukocyte TNFR1 and TNFR2 expression contributes to the peripheral immune response in cases with ischemic stroke. Cells 10(4). https://doi.org/10.3390/cells10040861

  61. Clausen BH, Wirenfeldt M, Høgedal SS, Frich LH, Nielsen HH, Schrøder HD, Østergaard K, Finsen B, et al (2020) Characterization of the TNF and IL-1 systems in human brain and blood after ischemic stroke. Acta Neuropathol Commun 8(1):81. https://doi.org/10.1186/s40478-020-00957-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kim HL, Lee JP, An JN, Kim JH, Lim WH, Seo JB, Chung WY, Oh YK, et al (2017) Soluble tumor necrosis factor receptors and arterial stiffness in patients with coronary atherosclerosis. Am J Hypertens 30(3):313–318. https://doi.org/10.1093/ajh/hpw134

    Article  CAS  PubMed  Google Scholar 

  63. Boehme AK, McClure LA, Zhang Y, Luna JM, Del Brutto OH, Benavente OR, Elkind MS (2016) Inflammatory markers and outcomes after lacunar stroke: levels of inflammatory markers in treatment of stroke study. Stroke 47(3):659–667. https://doi.org/10.1161/strokeaha.115.012166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lin SY, Wang YY, Chang CY, Wu CC, Chen WY, Liao SL, Chen CJ (2021) TNF-α receptor inhibitor alleviates metabolic and inflammatory changes in a rat model of ischemic stroke. Antioxidants (Basel) 10(6). https://doi.org/10.3390/antiox10060851

  65. Clausen BH, Degn M, Martin NA, Couch Y, Karimi L, Ormhøj M, Mortensen ML, Gredal HB, et al (2014) Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia. J Neuroinflammation 11:203. https://doi.org/10.1186/s12974-014-0203-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Clark IA (2020) Randomized controlled trial validating the use of perispinal etanercept to reduce post-stroke disability has wide-ranging implications. Expert Rev Neurother 20(3):203–205. https://doi.org/10.1080/14737175.2020.1727742

    Article  CAS  PubMed  Google Scholar 

  67. Duan R, Wang N, Shang Y, Li H, Liu Q, Li L, Zhao X (2022) TNF-α (G-308A) Polymorphism, circulating levels of TNF-α and IGF-1: risk factors for ischemic stroke-an updated meta-analysis. Front Aging Neurosci 14:831910. https://doi.org/10.3389/fnagi.2022.831910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wu JC, Zhang X, Wang JH, Liu QW, Wang XQ, Wu ZQ, Wang J, Zhang C, et al (2019) Gene polymorphisms and circulating levels of the TNF-alpha are associated with ischemic stroke: a meta-analysis based on 19,873 individuals. Int Immunopharmacol 75:105827. https://doi.org/10.1016/j.intimp.2019.105827

    Article  CAS  PubMed  Google Scholar 

  69. Macleod T, Berekmeri A, Bridgewood C, Stacey M, McGonagle D, Wittmann M (2021) The immunological impact of IL-1 family cytokines on the epidermal barrier. Front Immunol 12:808012. https://doi.org/10.3389/fimmu.2021.808012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Dinarello CA (2013) Overview of the interleukin-1 family of ligands and receptors. Semin Immunol 25(6):389–393. https://doi.org/10.1016/j.smim.2013.10.001

    Article  CAS  PubMed  Google Scholar 

  71. Satoh T, Otsuka A, Contassot E, French LE (2015) The inflammasome and IL-1β: implications for the treatment of inflammatory diseases. Immunotherapy 7(3):243–254. https://doi.org/10.2217/imt.14.106

    Article  CAS  PubMed  Google Scholar 

  72. Nayak AR, Kashyap RS, Kabra D, Purohit HJ, Taori GM, Daginawala HF (2012) Time course of inflammatory cytokines in acute ischemic stroke patients and their relation to inter-alfa trypsin inhibitor heavy chain 4 and outcome. Ann Indian Acad Neurol 15(3):181–185. https://doi.org/10.4103/0972-2327.99707

    Article  PubMed  PubMed Central  Google Scholar 

  73. Barnes J, Mondelli V, Pariante CM (2017) Genetic contributions of inflammation to depression. Neuropsychopharmacology 42(1):81–98. https://doi.org/10.1038/npp.2016.169

    Article  CAS  PubMed  Google Scholar 

  74. Yang J, Ma K, Zhang C, Liu Y, Liang F, Hu W, Bian X, Yang S, Fu X (2020) Burns impair blood-brain barrier and mesenchymal stem cells can reverse the process in mice. Front Immunol 11:578879. https://doi.org/10.3389/fimmu.2020.578879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Liu G, Tsuruta Y, Gao Z, Park YJ, Abraham E (2007) Variant IL-1 receptor-associated kinase-1 mediates increased NF-kappa B activity. J Immunol 179(6):4125–4134. https://doi.org/10.4049/jimmunol.179.6.4125

    Article  CAS  PubMed  Google Scholar 

  76. Cahill CM, Rogers JT (2008) Interleukin (IL) 1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IkappaB kinase alpha pathway targeting activator protein-1. J Biol Chem 283(38):25900–25912. https://doi.org/10.1074/jbc.M707692200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Chaparro-Huerta V, Rivera-Cervantes MC, Flores-Soto ME, Gómez-Pinedo U, Beas-Zárate C (2005) Proinflammatory cytokines and apoptosis following glutamate-induced excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats. J Neuroimmunol 165(1–2):53–62. https://doi.org/10.1016/j.jneuroim.2005.04.025

    Article  CAS  PubMed  Google Scholar 

  78. Li W, Zheng S, Tang C, Zhu Y, Wang X (2007) JNK-AP-1 pathway involved in interleukin-1beta-induced calcitonin gene-related peptide secretion in human type II alveolar epithelial cells. Peptides 28(6):1252–1259. https://doi.org/10.1016/j.peptides.2007.03.021

    Article  CAS  PubMed  Google Scholar 

  79. Cicolari S, Catapano AL, Magni P (2021) Inflammaging and neurodegenerative diseases: Role of NLRP3 inflammasome activation in brain atherosclerotic vascular disease. Mech Ageing Dev 195:111467. https://doi.org/10.1016/j.mad.2021.111467

    Article  CAS  PubMed  Google Scholar 

  80. Roth S, Cao J, Singh V, Tiedt S, Hundeshagen G, Li T, Boehme JD, Chauhan D, et al (2021) Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade. Immunity 54(4):648-659.e648. https://doi.org/10.1016/j.immuni.2021.02.004

    Article  CAS  PubMed  Google Scholar 

  81. Sharma BR, Karki R, Kanneganti TD (2019) Role of AIM2 inflammasome in inflammatory diseases, cancer and infection. Eur J Immunol 49(11):1998–2011. https://doi.org/10.1002/eji.201848070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Denes A, Pinteaux E, Rothwell NJ, Allan SM (2011) Interleukin-1 and stroke: biomarker, harbinger of damage, and therapeutic target. Cerebrovasc Dis 32(6):517–527. https://doi.org/10.1159/000332205

    Article  CAS  PubMed  Google Scholar 

  83. Protopsaltis J, Kokkoris S, Korantzopoulos P, Milionis HJ, Karzi E, Anastasopoulou A, Filioti K, Antonopoulos S, et al (2009) Prediction of long-term functional outcome in patients with acute ischemic non-embolic stroke. Atherosclerosis 203(1):228–235. https://doi.org/10.1016/j.atherosclerosis.2008.05.042

    Article  CAS  PubMed  Google Scholar 

  84. Becker KJ, Dankwa D, Lee R, Schulze J, Zierath D, Tanzi P, Cain K, Dressel A, et al (2014) Stroke, IL-1ra, IL1RN, infection and outcome. Neurocrit Care 21(1):140–146. https://doi.org/10.1007/s12028-013-9899-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Tanaka T, Narazaki M, Kishimoto T (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6(10):a016295. https://doi.org/10.1101/cshperspect.a016295

    Article  PubMed  PubMed Central  Google Scholar 

  86. Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Hallenbeck JM, del Zoppo GJ, et al (2003) An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol 139(1–2):93–101. https://doi.org/10.1016/s0165-5728(03)00134-6

    Article  CAS  PubMed  Google Scholar 

  87. Smith CJ, Emsley HC, Gavin CM, Georgiou RF, Vail A, Barberan EM, del Zoppo GJ, Hallenbeck JM, et al (2004) Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol 4:2. https://doi.org/10.1186/1471-2377-4-2

    Article  PubMed  PubMed Central  Google Scholar 

  88. Yao H, Zhang Y, Shu H, Xie B, Tao Y, Yuan Y, Shang Y, Yuan S, Zhang J (2019) Hyperforin promotes post-stroke neuroangiogenesis via astrocytic IL-6-mediated negative immune regulation in the ischemic brain. Front Cell Neurosci 13:201. https://doi.org/10.3389/fncel.2019.00201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Erta M, Quintana A, Hidalgo J (2012) Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 8(9):1254–1266. https://doi.org/10.7150/ijbs.4679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zeng L, Wang Y, Liu J, Wang L, Weng S, Chen K, Domino EF, Yang GY (2013) Pro-inflammatory cytokine network in peripheral inflammation response to cerebral ischemia. Neurosci Lett 548:4–9. https://doi.org/10.1016/j.neulet.2013.04.037

    Article  CAS  PubMed  Google Scholar 

  91. Mechtouff L, Bochaton T, Paccalet A, Da Silva CC, Buisson M, Amaz C, Derex L, Ong E, et al (2021) Association of interleukin-6 levels and futile reperfusion after mechanical thrombectomy. Neurology 96(5):e752–e757. https://doi.org/10.1212/wnl.0000000000011268

    Article  CAS  PubMed  Google Scholar 

  92. Jenny NS, Callas PW, Judd SE, McClure LA, Kissela B, Zakai NA, Cushman M (2019) Inflammatory cytokines and ischemic stroke risk: the REGARDS cohort. Neurology 92(20):e2375–e2384. https://doi.org/10.1212/wnl.0000000000007416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Armstead WM, Hekierski H, Pastor P, Yarovoi S, Higazi AA, Cines DB (2019) Release of IL-6 after stroke contributes to impaired cerebral autoregulation and hippocampal neuronal necrosis through NMDA receptor activation and upregulation of ET-1 and JNK. Transl Stroke Res 10(1):104–111. https://doi.org/10.1007/s12975-018-0617-z

    Article  CAS  PubMed  Google Scholar 

  94. Suzuki S, Tanaka K, Suzuki N (2009) Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophic aspects. J Cereb Blood Flow Metab 29(3):464–479. https://doi.org/10.1038/jcbfm.2008.141

    Article  CAS  PubMed  Google Scholar 

  95. Gertz K, Kronenberg G, Kälin RE, Baldinger T, Werner C, Balkaya M, Eom GD, Hellmann-Regen J, et al (2012) Essential role of interleukin-6 in post-stroke angiogenesis. Brain 135(Pt 6):1964–1980. https://doi.org/10.1093/brain/aws075

    Article  PubMed  PubMed Central  Google Scholar 

  96. Nguyen TV, Frye JB, Zbesko JC, Stepanovic K, Hayes M, Urzua A, Serrano G, Beach TG, et al (2016) Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue. Acta Neuropathol Commun 4(1):100. https://doi.org/10.1186/s40478-016-0371-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. de Bilbao F, Arsenijevic D, Moll T, Garcia-Gabay I, Vallet P, Langhans W, Giannakopoulos P (2009) In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice. J Neurochem 110(1):12–22. https://doi.org/10.1111/j.1471-4159.2009.06098.x

    Article  CAS  PubMed  Google Scholar 

  98. Pérez-de Puig I, Miró F, Salas-Perdomo A, Bonfill-Teixidor E, Ferrer-Ferrer M, Márquez-Kisinousky L, Planas AM (2013) IL-10 deficiency exacerbates the brain inflammatory response to permanent ischemia without preventing resolution of the lesion. J Cereb Blood Flow Metab 33(12):1955–1966. https://doi.org/10.1038/jcbfm.2013.155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Sharma S, Yang B, Xi X, Grotta JC, Aronowski J, Savitz SI (2011) IL-10 directly protects cortical neurons by activating PI-3 kinase and STAT-3 pathways. Brain Res 1373:189–194. https://doi.org/10.1016/j.brainres.2010.11.096

    Article  CAS  PubMed  Google Scholar 

  100. Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius AJ (2004) Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity: a role for p50. Clin Exp Immunol 135(1):64–73. https://doi.org/10.1111/j.1365-2249.2004.02342.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bodhankar S, Chen Y, Vandenbark AA, Murphy SJ, Offner H (2013) IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke. Metab Brain Dis 28(3):375–386. https://doi.org/10.1007/s11011-013-9413-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wang J, Xie L, Yang C, Ren C, Zhou K, Wang B, Zhang Z, Wang Y, et al (2015) Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10. Front Cell Neurosci 9:361. https://doi.org/10.3389/fncel.2015.00361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Liesz A, Zhou W, Na SY, Hämmerling GJ, Garbi N, Karcher S, Mracsko E, Backs J, et al (2013) Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. J Neurosci 33(44):17350–17362. https://doi.org/10.1523/jneurosci.4901-12.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Kleinschnitz C, Kraft P, Dreykluft A, Hagedorn I, Göbel K, Schuhmann MK, Langhauser F, Helluy X, et al (2013) Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood 121(4):679–691. https://doi.org/10.1182/blood-2012-04-426734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Nolan KF, Greaves DR, Waldmann H (1998) The human interleukin 18 gene IL18 maps to 11q22.2–q22.3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci. Genomics 51(1):161–163. https://doi.org/10.1006/geno.1998.5336

    Article  CAS  PubMed  Google Scholar 

  106. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378(6552):88–91. https://doi.org/10.1038/378088a0

    Article  CAS  PubMed  Google Scholar 

  107. Swain SL (2001) Interleukin 18: tipping the balance towards a T helper cell 1 response. J Exp Med 194(3):F11-14. https://doi.org/10.1084/jem.194.3.f11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Hao Y, Ding J, Hong R, Bai S, Wang Z, Mo C, Hu Q, Li Z, et al (2019) Increased interleukin-18 level contributes to the development and severity of ischemic stroke. Aging (Albany NY) 11(18):7457–7472. https://doi.org/10.18632/aging.102253

    Article  CAS  PubMed  Google Scholar 

  109. Ihim SA, Abubakar SD, Zian Z, Sasaki T, Saffarioun M, Maleknia S, Azizi G (2022) Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: biological role in induction, regulation, and treatment. Front Immunol 13:919973. https://doi.org/10.3389/fimmu.2022.919973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Gurung P, Lukens JR, Kanneganti TD (2015) Mitochondria: diversity in the regulation of the NLRP3 inflammasome. Trends Mol Med 21(3):193–201. https://doi.org/10.1016/j.molmed.2014.11.008

    Article  CAS  PubMed  Google Scholar 

  111. Bossaller L, Chiang PI, Schmidt-Lauber C, Ganesan S, Kaiser WJ, Rathinam VA, Mocarski ES, Subramanian D, et al (2012) Cutting edge: FAS (CD95) mediates noncanonical IL-1β and IL-18 maturation via caspase-8 in an RIP3-independent manner. J Immunol 189(12):5508–5512. https://doi.org/10.4049/jimmunol.1202121

    Article  CAS  PubMed  Google Scholar 

  112. Sugawara S, Uehara A, Nochi T, Yamaguchi T, Ueda H, Sugiyama A, Hanzawa K, Kumagai K, et al (2001) Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells. J Immunol 167(11):6568–6575. https://doi.org/10.4049/jimmunol.167.11.6568

    Article  CAS  PubMed  Google Scholar 

  113. Omoto Y, Tokime K, Yamanaka K, Habe K, Morioka T, Kurokawa I, Tsutsui H, Yamanishi K, et al (2006) Human mast cell chymase cleaves pro-IL-18 and generates a novel and biologically active IL-18 fragment. J Immunol 177(12):8315–8319. https://doi.org/10.4049/jimmunol.177.12.8315

    Article  CAS  PubMed  Google Scholar 

  114. Omoto Y, Yamanaka K, Tokime K, Kitano S, Kakeda M, Akeda T, Kurokawa I, Gabazza EC, et al (2010) Granzyme B is a novel interleukin-18 converting enzyme. J Dermatol Sci 59(2):129–135. https://doi.org/10.1016/j.jdermsci.2010.05.004

    Article  CAS  PubMed  Google Scholar 

  115. Rackov G, Tavakoli Zaniani P, Colomo Del Pino S, Shokri R, Monserrat J, Alvarez-Mon M, Martinez AC, Balomenos D (2022) Mitochondrial reactive oxygen is critical for IL-12/IL-18-induced IFN-γ production by CD4(+) T cells and is regulated by Fas/FasL signaling. Cell Death Dis 13(6):531. https://doi.org/10.1038/s41419-022-04907-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Ding H, Li Y, Wen M, Liu X, Han Y, Zeng H (2021) Elevated intracranial pressure induces IL-1β and IL-18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats. Int J Mol Med 47(1):183–194. https://doi.org/10.3892/ijmm.2020.4779

    Article  CAS  PubMed  Google Scholar 

  117. Shi JH, Niu LD, Chen XY, Hou JY, Yang P, Li GP (2015) Investigation on the IL-18 -607A/C and -137C/G on the susceptibility of ischemic stroke. Pak J Med Sci 31(1):198–202. https://doi.org/10.12669/pjms.311.5997

    Article  PubMed  PubMed Central  Google Scholar 

  118. Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302(5651):1760–1765. https://doi.org/10.1126/science.1088417

    Article  CAS  PubMed  Google Scholar 

  119. Borsini A, Cattaneo A, Malpighi C, Thuret S, Harrison NA, Zunszain PA, Pariante CM (2018) Interferon-alpha reduces human hippocampal neurogenesis and increases apoptosis via activation of distinct STAT1-dependent mechanisms. Int J Neuropsychopharmacol 21(2):187–200. https://doi.org/10.1093/ijnp/pyx083

    Article  CAS  PubMed  Google Scholar 

  120. Bolshakov AP, Tret’yakova LV, Kvichansky AA, Gulyaeva NV (2021) Glucocorticoids: Dr. Jekyll and Mr. Hyde of hippocampal neuroinflammation. Biochemistry (Mosc) 86(2):156–167. https://doi.org/10.1134/s0006297921020048

    Article  CAS  PubMed  Google Scholar 

  121. Gulyaeva NV (2019) Functional neurochemistry of the ventral and dorsal hippocampus: stress, depression, dementia and remote hippocampal damage. Neurochem Res 44(6):1306–1322. https://doi.org/10.1007/s11064-018-2662-0

    Article  CAS  PubMed  Google Scholar 

  122. Schmaal L, Veltman DJ, van Erp TG, Sämann PG, Frodl T, Jahanshad N, Loehrer E, Tiemeier H, et al (2016) Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. Mol Psychiatry 21(6):806–812. https://doi.org/10.1038/mp.2015.69

    Article  CAS  PubMed  Google Scholar 

  123. Woelfer M, Kasties V, Kahlfuss S, Walter M (2019) The role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder. Neuroscience 403:93–110. https://doi.org/10.1016/j.neuroscience.2018.03.034

    Article  CAS  PubMed  Google Scholar 

  124. Troubat R, Barone P, Leman S, Desmidt T, Cressant A, Atanasova B, Brizard B, El Hage W, et al (2021) Neuroinflammation and depression: a review. Eur J Neurosci 53(1):151–171. https://doi.org/10.1111/ejn.14720

    Article  CAS  PubMed  Google Scholar 

  125. Christensen K, Murray JC (2007) What genome-wide association studies can do for medicine. N Engl J Med 356(11):1094–1097. https://doi.org/10.1056/NEJMp068126

    Article  CAS  PubMed  Google Scholar 

  126. Smith AJ, Humphries SE (2009) Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev 20(1):43–59. https://doi.org/10.1016/j.cytogfr.2008.11.006

    Article  CAS  PubMed  Google Scholar 

  127. Capuron L, Fornwalt FB, Knight BT, Harvey PD, Ninan PT, Miller AH (2009) Does cytokine-induced depression differ from idiopathic major depression in medically healthy individuals? J Affect Disord 119(1–3):181–185. https://doi.org/10.1016/j.jad.2009.02.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Zou W, Feng R, Yang Y (2018) Changes in the serum levels of inflammatory cytokines in antidepressant drug-naïve patients with major depression. PLoS One 13(6):e0197267. https://doi.org/10.1371/journal.pone.0197267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Enache D, Pariante CM, Mondelli V (2019) Markers of central inflammation in major depressive disorder: a systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain Behav Immun 81:24–40. https://doi.org/10.1016/j.bbi.2019.06.015

    Article  PubMed  Google Scholar 

  130. Haroon E, Woolwine BJ, Chen X, Pace TW, Parekh S, Spivey JR, Hu XP, Miller AH (2014) IFN-alpha-induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy. Neuropsychopharmacology 39(7):1777–1785. https://doi.org/10.1038/npp.2014.25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Cheng Y, Desse S, Martinez A, Worthen RJ, Jope RS, Beurel E (2018) TNFα disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice. Brain Behav Immun 69:556–567. https://doi.org/10.1016/j.bbi.2018.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Liu H, Luiten PG, Eisel UL, Dejongste MJ, Schoemaker RG (2013) Depression after myocardial infarction: TNF-α-induced alterations of the blood-brain barrier and its putative therapeutic implications. Neurosci Biobehav Rev 37(4):561–572. https://doi.org/10.1016/j.neubiorev.2013.02.004

    Article  CAS  PubMed  Google Scholar 

  133. Zou JY, Crews FT (2005) TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res 1034(1–2):11–24. https://doi.org/10.1016/j.brainres.2004.11.014

    Article  CAS  PubMed  Google Scholar 

  134. Levine J, Barak Y, Chengappa KN, Rapoport A, Rebey M, Barak V (1999) Cerebrospinal cytokine levels in patients with acute depression. Neuropsychobiology 40(4):171–176. https://doi.org/10.1159/000026615

    Article  CAS  PubMed  Google Scholar 

  135. Thomas AJ, Davis S, Morris C, Jackson E, Harrison R, O’Brien JT (2005) Increase in interleukin-1beta in late-life depression. Am J Psychiatry 162(1):175–177. https://doi.org/10.1176/appi.ajp.162.1.175

    Article  PubMed  Google Scholar 

  136. Ferreira AM, Leal B, Ferreira I, Brás S, Moreira I, Samões R, Sousa AP, Santos E, et al (2021) Depression and anxiety in multiple sclerosis patients: the role of genetic variability of interleukin 1β. Mult Scler Relat Disord 52:102982. https://doi.org/10.1016/j.msard.2021.102982

    Article  CAS  PubMed  Google Scholar 

  137. Yue N, Huang H, Zhu X, Han Q, Wang Y, Li B, Liu Q, Wu G, et al (2017) Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors. J Neuroinflammation 14(1):102. https://doi.org/10.1186/s12974-017-0865-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Seil M, El Ouaaliti M, Abdou Foumekoye S, Pochet S, Dehaye JP (2012) Distinct regulation by lipopolysaccharides of the expression of interleukin-1β by murine macrophages and salivary glands. Innate Immun 18(1):14–24. https://doi.org/10.1177/1753425910377101

    Article  CAS  PubMed  Google Scholar 

  139. Clark AK, Staniland AA, Marchand F, Kaan TK, McMahon SB, Malcangio M (2010) P2X7-dependent release of interleukin-1beta and nociception in the spinal cord following lipopolysaccharide. J Neurosci 30(2):573–582. https://doi.org/10.1523/jneurosci.3295-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Ribeiro DE, Roncalho AL, Glaser T, Ulrich H, Wegener G, Joca S (2019) P2X7 receptor signaling in stress and depression. Int J Mol Sci 20(11). https://doi.org/10.3390/ijms20112778

  141. Ovaskainen Y, Koponen H, Jokelainen J, Keinänen-Kiukaanniemi S, Kumpusalo E, Vanhala M (2009) Depressive symptomatology is associated with decreased interleukin-1 beta and increased interleukin-1 receptor antagonist levels in males. Psychiatry Res 167(1–2):73–79. https://doi.org/10.1016/j.psychres.2007.12.004

    Article  CAS  PubMed  Google Scholar 

  142. Rothermundt M, Arolt V, Peters M, Gutbrodt H, Fenker J, Kersting A, Kirchner H (2001) Inflammatory markers in major depression and melancholia. J Affect Disord 63(1–3):93–102. https://doi.org/10.1016/s0165-0327(00)00157-9

    Article  CAS  PubMed  Google Scholar 

  143. Kagaya A, Kugaya A, Takebayashi M, Fukue-Saeki M, Saeki T, Yamawaki S, Uchitomi Y (2001) Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan. Neuropsychobiology 43(2):59–62. https://doi.org/10.1159/000054867

    Article  CAS  PubMed  Google Scholar 

  144. Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS (2010) Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci U S A 107(6):2669–2674. https://doi.org/10.1073/pnas.0910658107

    Article  PubMed  PubMed Central  Google Scholar 

  145. Alcocer-Gómez E, Ulecia-Morón C, Marín-Aguilar F, Rybkina T, Casas-Barquero N, Ruiz-Cabello J, Ryffel B, Apetoh L, Ghiringhelli F, et al (2016) Stress-induced depressive behaviors require a functional NLRP3 inflammasome. Mol Neurobiol 53(7):4874–4882. https://doi.org/10.1007/s12035-015-9408-7

    Article  CAS  PubMed  Google Scholar 

  146. Zhou L, Zhang J, Han X, Fang J, Zhou S, Lu L, Shi Q, Ying H (2022) CysLT(2)R antagonist HAMI 3379 ameliorates post-stroke depression through NLRP3 inflammasome/pyroptosis pathway in gerbils. Brain Sci 12(8). https://doi.org/10.3390/brainsci12080976

  147. Kitaoka S (2022) Inflammation in the brain and periphery found in animal models of depression and its behavioral relevance. J Pharmacol Sci 148(2):262–266. https://doi.org/10.1016/j.jphs.2021.12.005

    Article  CAS  PubMed  Google Scholar 

  148. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457. https://doi.org/10.1016/j.biopsych.2009.09.033

    Article  CAS  PubMed  Google Scholar 

  149. Haapakoski R, Mathieu J, Ebmeier KP, Alenius H, Kivimäki M (2015) Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain Behav Immun 49:206–215. https://doi.org/10.1016/j.bbi.2015.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Hodes GE, Ménard C, Russo SJ (2016) Integrating interleukin-6 into depression diagnosis and treatment. Neurobiol Stress 4:15–22. https://doi.org/10.1016/j.ynstr.2016.03.003

    Article  PubMed  PubMed Central  Google Scholar 

  151. Chourbaji S, Urani A, Inta I, Sanchis-Segura C, Brandwein C, Zink M, Schwaninger M, Gass P (2006) IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiol Dis 23(3):587–594. https://doi.org/10.1016/j.nbd.2006.05.001

    Article  CAS  PubMed  Google Scholar 

  152. Jeon SW, Kim YK (2016) Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? World J Psychiatry 6(3):283–293. https://doi.org/10.5498/wjp.v6.i3.283

    Article  PubMed  PubMed Central  Google Scholar 

  153. Girotti M, Donegan JJ, Morilak DA (2013) Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress. Psychoneuroendocrinology 38(7):1158–1169. https://doi.org/10.1016/j.psyneuen.2012.11.004

    Article  CAS  PubMed  Google Scholar 

  154. Ting EY, Yang AC, Tsai SJ (2020) Role of interleukin-6 in depressive disorder. Int J Mol Sci 21(6). https://doi.org/10.3390/ijms21062194

  155. Anderson G, Kubera M, Duda W, Lasoń W, Berk M, Maes M (2013) Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway, melatonin and neuroprogression. Pharmacol Rep 65(6):1647–1654. https://doi.org/10.1016/s1734-1140(13)71526-3

    Article  CAS  PubMed  Google Scholar 

  156. Leonard BE (2018) Inflammation and depression: a causal or coincidental link to the pathophysiology? Acta Neuropsychiatr 30(1):1–16. https://doi.org/10.1017/neu.2016.69

    Article  PubMed  Google Scholar 

  157. Lima Giacobbo B, Doorduin J, Klein HC, Dierckx R, Bromberg E, de Vries EFJ (2019) Brain-derived neurotrophic factor in brain disorders: focus on neuroinflammation. Mol Neurobiol 56(5):3295–3312. https://doi.org/10.1007/s12035-018-1283-6

    Article  CAS  PubMed  Google Scholar 

  158. Belge JB, van Diermen L, Sabbe B, Parizel P, Morrens M, Coppens V, Constant E, de Timary P, et al (2020) Inflammation, hippocampal volume, and therapeutic outcome following electroconvulsive therapy in depressive patients: a pilot study. Neuropsychobiology 79(3):222–232. https://doi.org/10.1159/000506133

    Article  CAS  PubMed  Google Scholar 

  159. Zhou YL, Wu FC, Wang CY, Zheng W, Lan XF, Deng XR, Ning YP (2020) Relationship between hippocampal volume and inflammatory markers following six infusions of ketamine in major depressive disorder. J Affect Disord 276:608–615. https://doi.org/10.1016/j.jad.2020.06.068

    Article  CAS  PubMed  Google Scholar 

  160. Salvadore G, Nugent AC, Lemaitre H, Luckenbaugh DA, Tinsley R, Cannon DM, Neumeister A, Zarate CA Jr, et al (2011) Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder. Neuroimage 54(4):2643–2651. https://doi.org/10.1016/j.neuroimage.2010.11.011

    Article  PubMed  Google Scholar 

  161. Koolschijn PC, van Haren NE, Lensvelt-Mulders GJ, Hulshoff Pol HE, Kahn RS (2009) Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 30(11):3719–3735. https://doi.org/10.1002/hbm.20801

    Article  PubMed  PubMed Central  Google Scholar 

  162. Kennedy SH, Evans KR, Krüger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ (2001) Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 158(6):899–905. https://doi.org/10.1176/appi.ajp.158.6.899

    Article  CAS  PubMed  Google Scholar 

  163. Kakeda S, Watanabe K, Katsuki A, Sugimoto K, Igata N, Ueda I, Igata R, Abe O, Yoshimura R, Korogi Y (2018) Relationship between interleukin (IL)-6 and brain morphology in drug-naïve, first-episode major depressive disorder using surface-based morphometry. Sci Rep 8(1):10054. https://doi.org/10.1038/s41598-018-28300-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, Hashimoto K (2017) Blockade of interleukin-6 receptor in the periphery promotes rapid and sustained antidepressant actions: a possible role of gut-microbiota-brain axis. Transl Psychiatry 7(5):e1138. https://doi.org/10.1038/tp.2017.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Khandaker GM, Oltean BP, Kaser M, Dibben CRM, Ramana R, Jadon DR, Dantzer R, Coles AJ, Lewis G, Jones PB (2018) Protocol for the insight study: a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation. BMJ Open 8(9):e025333. https://doi.org/10.1136/bmjopen-2018-025333

    Article  PubMed  PubMed Central  Google Scholar 

  166. Zhanina MY, Druzhkova TA, Yakovlev AA, Vladimirova EE, Freiman SV, Eremina NN, Guekht AB, Gulyaeva NV (2022) Development of post-stroke cognitive and depressive disturbances: associations with neurohumoral indices. Curr Issues Mol Biol 44(12):6290–6305. https://doi.org/10.3390/cimb44120429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Cui Y, Ma G, Kong F, Song L (2021) Diagnostic values of miR-221-3p in serum and cerebrospinal fluid for post-stroke depression and analysis of risk factors. Iran J Public Health 50(6):1241–1249. https://doi.org/10.18502/ijph.v50i6.6423

    Article  PubMed  PubMed Central  Google Scholar 

  168. Dhabhar FS, Burke HM, Epel ES, Mellon SH, Rosser R, Reus VI, Wolkowitz OM (2009) Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression. J Psychiatr Res 43(11):962–969. https://doi.org/10.1016/j.jpsychires.2009.05.010

    Article  PubMed  Google Scholar 

  169. Euteneuer F, Dannehl K, Del Rey A, Engler H, Schedlowski M, Rief W (2017) Peripheral immune alterations in major depression: the role of subtypes and pathogenetic characteristics. Front Psychiatry 8:250. https://doi.org/10.3389/fpsyt.2017.00250

    Article  PubMed  PubMed Central  Google Scholar 

  170. Wiener CD, Moreira FP, Portela LV, Strogulski NR, Lara DR, da Silva RA, Souza LDM, Jansen K, Oses JP (2019) Interleukin-6 and interleukin-10 in mood disorders: a population-based study. Psychiatry Res 273:685–689. https://doi.org/10.1016/j.psychres.2019.01.100

    Article  CAS  PubMed  Google Scholar 

  171. Al-Fadhel SZ, Al-Hakeim HK, Al-Dujaili AH, Maes M (2019) IL-10 is associated with increased mu-opioid receptor levels in major depressive disorder. Eur Psychiatry 57:46–51. https://doi.org/10.1016/j.eurpsy.2018.10.001

    Article  PubMed  Google Scholar 

  172. Laumet G, Edralin JD, Chiang AC, Dantzer R, Heijnen CJ, Kavelaars A (2018) Resolution of inflammation-induced depression requires T lymphocytes and endogenous brain interleukin-10 signaling. Neuropsychopharmacology 43(13):2597–2605. https://doi.org/10.1038/s41386-018-0154-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Zhang HY, Wang Y, He Y, Wang T, Huang XH, Zhao CM, Zhang L, Li SW, Wang C, Qu YN, Jiang XX (2020) A1 astrocytes contribute to murine depression-like behavior and cognitive dysfunction, which can be alleviated by IL-10 or fluorocitrate treatment. J Neuroinflammation 17(1):200. https://doi.org/10.1186/s12974-020-01871-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Langhein M, Seitz-Holland J, Lyall AE, Pasternak O, Chunga N, Cetin-Karayumak S, Kubicki A, Mulert C, Espinoza RT, Narr KL, Kubicki M (2022) Association between peripheral inflammation and free-water imaging in major depressive disorder before and after ketamine treatment - a pilot study. J Affect Disord 314:78–85. https://doi.org/10.1016/j.jad.2022.06.043

    Article  CAS  PubMed  Google Scholar 

  175. Norden DM, Fenn AM, Dugan A, Godbout JP (2014) TGFβ produced by IL-10 redirected astrocytes attenuates microglial activation. Glia 62(6):881–895. https://doi.org/10.1002/glia.22647

    Article  PubMed  PubMed Central  Google Scholar 

  176. Ormstad H, Aass HC, Amthor KF, Lund-Sørensen N, Sandvik L (2012) Serum levels of cytokines, glucose, and hemoglobin as possible predictors of poststroke depression, and association with poststroke fatigue. Int J Neurosci 122(11):682–690. https://doi.org/10.3109/00207454.2012.709892

    Article  CAS  PubMed  Google Scholar 

  177. Al-Hakeim HK, Al-Rammahi DA, Al-Dujaili AH (2015) IL-6, IL-18, sIL-2R, and TNFα proinflammatory markers in depression and schizophrenia patients who are free of overt inflammation. J Affect Disord 182:106–114. https://doi.org/10.1016/j.jad.2015.04.044

    Article  CAS  PubMed  Google Scholar 

  178. Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O (2013) Neuroinflammation and psychiatric illness. J Neuroinflammation 10:43. https://doi.org/10.1186/1742-2094-10-43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Yirmiya R, Rimmerman N, Reshef R (2015) Depression as a microglial disease. Trends Neurosci 38(10):637–658. https://doi.org/10.1016/j.tins.2015.08.001

    Article  CAS  PubMed  Google Scholar 

  180. Alcocer-Gómez E, de Miguel M, Casas-Barquero N, Núñez-Vasco J, Sánchez-Alcazar JA, Fernández-Rodríguez A, Cordero MD (2014) NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav Immun 36:111–117. https://doi.org/10.1016/j.bbi.2013.10.017

    Article  CAS  PubMed  Google Scholar 

  181. Sugama S, Conti B (2008) Interleukin-18 and stress. Brain Res Rev 58(1):85–95. https://doi.org/10.1016/j.brainresrev.2007.11.003

    Article  CAS  PubMed  Google Scholar 

  182. McKay LI, Cidlowski JA (1999) Molecular control of immune/inflammatory responses: interactions between nuclear factor-kappa B and steroid receptor-signaling pathways. Endocr Rev 20(4):435–459. https://doi.org/10.1210/edrv.20.4.0375

    Article  CAS  PubMed  Google Scholar 

  183. Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31(9):464–468. https://doi.org/10.1016/j.tins.2008.06.006

    Article  CAS  PubMed  Google Scholar 

  184. Yamanishi K, Doe N, Mukai K, Ikubo K, Hashimoto T, Uwa N, Sumida M, El-Darawish Y, Gamachi N, et al (2019) Interleukin-18-deficient mice develop hippocampal abnormalities related to possible depressive-like behaviors. Neuroscience 408:147–160. https://doi.org/10.1016/j.neuroscience.2019.04.003

    Article  CAS  PubMed  Google Scholar 

  185. Fan N, Luo Y, Ou Y, He H (2017) Altered serum levels of TNF-α, IL-6, and IL-18 in depressive disorder patients. Hum Psychopharmacol 32(4). https://doi.org/10.1002/hup.2588

  186. Spalletta G, Bossù P, Ciaramella A, Bria P, Caltagirone C, Robinson RG (2006) The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines. Mol Psychiatry 11(11):984–991. https://doi.org/10.1038/sj.mp.4001879

    Article  CAS  PubMed  Google Scholar 

  187. Huang Y, Chen S, Luo Y, Han Z (2020) Crosstalk between Inflammation and the BBB in stroke. Curr Neuropharmacol 18(12):1227–1236. https://doi.org/10.2174/1570159x18666200620230321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Wu S, Yin Y, Du L (2022) Blood-brain barrier dysfunction in the pathogenesis of major depressive disorder. Cell Mol Neurobiol 42(8):2571–2591. https://doi.org/10.1007/s10571-021-01153-9

    Article  PubMed  Google Scholar 

  189. Zhang L, Zhang J, You Z (2018) Switching of the microglial activation phenotype is a possible treatment for depression disorder. Front Cell Neurosci 12:306. https://doi.org/10.3389/fncel.2018.00306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Wang H, He Y, Sun Z, Ren S, Liu M, Wang G, Yang J (2022) Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression. J Neuroinflammation 19(1):132. https://doi.org/10.1186/s12974-022-02492-0

    Article  PubMed  PubMed Central  Google Scholar 

  191. Kaufmann FN, Costa AP, Ghisleni G, Diaz AP, Rodrigues ALS, Peluffo H, Kaster MP (2017) NLRP3 inflammasome-driven pathways in depression: clinical and preclinical findings. Brain Behav Immun 64:367–383. https://doi.org/10.1016/j.bbi.2017.03.002

    Article  CAS  PubMed  Google Scholar 

  192. Li C, Xu X, Wang Z, Wang Y, Luo L, Cheng J, Chen SF, Liu H, Wan Q, Wang Q (2020) Exercise ameliorates post-stroke depression by inhibiting PTEN elevation-mediated upregulation of TLR4/NF-κB/NLRP3 signaling in mice. Brain Res 1736:146777. https://doi.org/10.1016/j.brainres.2020.146777

    Article  CAS  PubMed  Google Scholar 

  193. Miller AH, Haroon E, Raison CL, Felger JC (2013) Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress Anxiety 30(4):297–306. https://doi.org/10.1002/da.22084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Myint AM, Kim YK (2003) Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses 61(5–6):519–525. https://doi.org/10.1016/s0306-9877(03)00207-x

    Article  CAS  PubMed  Google Scholar 

  195. Hamon M, Blier P (2013) Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry 45:54–63. https://doi.org/10.1016/j.pnpbp.2013.04.009

    Article  CAS  PubMed  Google Scholar 

  196. Kim YK, Won E (2017) The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder. Behav Brain Res 329:6–11. https://doi.org/10.1016/j.bbr.2017.04.020

    Article  CAS  PubMed  Google Scholar 

  197. Chen H, Huang X, Zeng C, Sun D, Liu F, Zhang J, Liao Q, Luo S, et al (2023) The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression. Front Immunol 14:1125634. https://doi.org/10.3389/fimmu.2023.1125634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. van Horssen J, van Schaik P, Witte M (2019) Inflammation and mitochondrial dysfunction: a vicious circle in neurodegenerative disorders? Neurosci Lett 710:132931. https://doi.org/10.1016/j.neulet.2017.06.050

    Article  CAS  PubMed  Google Scholar 

  199. Abcouwer SF, Shanmugam S, Gomez PF, Shushanov S, Barber AJ, Lanoue KF, Quinn PG, Kester M, Gardner TW (2008) Effect of IL-1beta on survival and energy metabolism of R28 and RGC-5 retinal neurons. Invest Ophthalmol Vis Sci 49(12):5581–5592. https://doi.org/10.1167/iovs.07-1032

    Article  PubMed  Google Scholar 

  200. Nabavi SF, Dean OM, Turner A, Sureda A, Daglia M, Nabavi SM (2015) Oxidative stress and post-stroke depression: possible therapeutic role of polyphenols? Curr Med Chem 22(3):343–351

    Article  CAS  PubMed  Google Scholar 

  201. Robinson RG, Jorge RE (2016) Post-stroke depression: a review. Am J Psychiatry 173(3):221–231. https://doi.org/10.1176/appi.ajp.2015.15030363

    Article  PubMed  Google Scholar 

  202. Legg LA, Rudberg AS, Hua X, Wu S, Hackett ML, Tilney R, Lindgren L, Kutlubaev MA, et al (2021) Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev 11(11):Cd009286. https://doi.org/10.1002/14651858.CD009286.pub4

    Article  PubMed  Google Scholar 

  203. Legg LA, Tilney R, Hsieh CF, Wu S, Lundström E, Rudberg AS, Kutlubaev MA, Dennis M, et al (2019) Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev 2019(11). https://doi.org/10.1002/14651858.CD009286.pub3

  204. Fang M, Zhong L, Jin X, Cui R, Yang W, Gao S, Lv J, Li B, et al (2019) Effect of inflammation on the process of stroke rehabilitation and poststroke depression. Front Psych 10. https://doi.org/10.3389/fpsyt.2019.00184

  205. Kappelmann N, Lewis G, Dantzer R, Jones PB, Khandaker GM (2018) Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry 23(2):335–343. https://doi.org/10.1038/mp.2016.167

    Article  CAS  PubMed  Google Scholar 

  206. Simen BB, Duman CH, Simen AA, Duman RS (2006) TNFalpha signaling in depression and anxiety: behavioral consequences of individual receptor targeting. Biol Psychiatry 59(9):775–785. https://doi.org/10.1016/j.biopsych.2005.10.013

    Article  CAS  PubMed  Google Scholar 

  207. Uzzan S, Azab AN (2021) Anti-TNF-α compounds as a treatment for depression. Molecules 26(8). https://doi.org/10.3390/molecules26082368

  208. Meroni PL, Valentini G, Ayala F, Cattaneo A, Valesini G (2015) New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors: a systematic analysis. Autoimmun Rev 14(9):812–829. https://doi.org/10.1016/j.autrev.2015.05.001

    Article  CAS  PubMed  Google Scholar 

  209. Ma K, Zhang H, Baloch Z (2016) Pathogenetic and therapeutic applications of tumor necrosis factor-α (TNF-α) in major depressive disorder: a systematic review. Int J Mol Sci 17(5). https://doi.org/10.3390/ijms17050733

  210. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiat 70(1):31–41. https://doi.org/10.1001/2013.jamapsychiatry.4

    Article  CAS  Google Scholar 

  211. O’Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, Lestage J, Castanon N, Kelley KW, Dantzer R (2009) Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci 29(13):4200–4209. https://doi.org/10.1523/jneurosci.5032-08.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Sun Y, Wang D, Salvadore G, Hsu B, Curran M, Casper C, Vermeulen J, Kent JM, Singh J, Drevets WC, Wittenberg GM, Chen G (2017) The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anhedonia in patients with rheumatoid arthritis and multicentric Castleman’s disease. Brain Behav Immun 66:156–164. https://doi.org/10.1016/j.bbi.2017.06.014

    Article  CAS  PubMed  Google Scholar 

  213. Worthen RJ, Garzon Zighelboim SS, Torres Jaramillo CS, Beurel E (2020) Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice. J Neuroinflammation 17(1):246. https://doi.org/10.1186/s12974-020-01922-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Novick D, Kim SH, Fantuzzi G, Reznikov LL, Dinarello CA, Rubinstein M (1999) Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response. Immunity 10(1):127–136. https://doi.org/10.1016/s1074-7613(00)80013-8

    Article  CAS  PubMed  Google Scholar 

  215. Schultz N, Hasseldam H, Rasmussen RS, Vindegaard N, McWilliam O, Iversen HK, Johansen FF (2019) Statin treatment before stroke reduces pro-inflammatory cytokine levels after stroke. Neurol Res 41(4):289–297. https://doi.org/10.1080/01616412.2018.1558000

    Article  CAS  PubMed  Google Scholar 

  216. Jin Z, Liang J, Wang J, Kolattukudy PE (2015) MCP-induced protein 1 mediates the minocycline-induced neuroprotection against cerebral ischemia/reperfusion injury in vitro and in vivo. J Neuroinflammation 12:39. https://doi.org/10.1186/s12974-015-0264-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Camargos QM, Silva BC, Silva DG, Toscano ECB, Oliveira BDS, Bellozi PMQ, Jardim BLO, Vieira ÉLM, et al (2020) Minocycline treatment prevents depression and anxiety-like behaviors and promotes neuroprotection after experimental ischemic stroke. Brain Res Bull 155:1–10. https://doi.org/10.1016/j.brainresbull.2019.11.009

    Article  CAS  PubMed  Google Scholar 

  218. La Russa D, Di Santo C, Lizasoain I, Moraga A, Bagetta G, Amantea D (2023) Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6): a promising immunomodulatory target in acute neurodegenerative diseases. Int J Mol Sci 24(2). https://doi.org/10.3390/ijms24021162

  219. Zhao H, Wang J, Gao L, Wang R, Liu X, Gao Z, Tao Z, Xu C, et al (2013) MiRNA-424 protects against permanent focal cerebral ischemia injury in mice involving suppressing microglia activation. Stroke 44(6):1706–1713. https://doi.org/10.1161/strokeaha.111.000504

    Article  CAS  PubMed  Google Scholar 

  220. Suento WJ, Kunisawa K, Wulaer B, Kosuge A, Iida T, Fujigaki S, Fujigaki H, Yamamoto Y, et al (2021) Prefrontal cortex miR-874-3p prevents lipopolysaccharide-induced depression-like behavior through inhibition of indoleamine 2,3-dioxygenase 1 expression in mice. J Neurochem 157(6):1963–1978. https://doi.org/10.1111/jnc.15222

    Article  CAS  PubMed  Google Scholar 

  221. Partoazar A, Seyyedian Z, Zamanian G, Saffari PM, Muhammadnejad A, Dehpour AR, Goudarzi R (2021) Neuroprotective phosphatidylserine liposomes alleviate depressive-like behavior related to stroke through neuroinflammation attenuation in the mouse hippocampus. Psychopharmacology 238(6):1531–1539. https://doi.org/10.1007/s00213-021-05783-1

    Article  CAS  PubMed  Google Scholar 

  222. Walter HL, van der Maten G, Antunes AR, Wieloch T, Ruscher K (2015) Treatment with AMD3100 attenuates the microglial response and improves outcome after experimental stroke. J Neuroinflammation 12:24. https://doi.org/10.1186/s12974-014-0232-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Zhao Y, Lee JH, Chen D, Gu X, Caslin A, Li J, Yu SP, Wei L (2017) DL-3-n-butylphthalide induced neuroprotection, regenerative repair, functional recovery and psychological benefits following traumatic brain injury in mice. Neurochem Int 111:82–92. https://doi.org/10.1016/j.neuint.2017.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Yin Q, Du T, Yang C, Li X, Zhao Z, Liu R, Yang B, Liu B (2021) Gadd45b is a novel mediator of depression-like behaviors and neuroinflammation after cerebral ischemia. Biochem Biophys Res Commun 554:107–113. https://doi.org/10.1016/j.bbrc.2021.03.104

    Article  CAS  PubMed  Google Scholar 

  225. Perrain R, Mekaoui L, Calvet D, Mas JL, Gorwood P (2020) A meta-analysis of poststroke depression risk factors comparing depressive-related factors versus others. Int Psychogeriatr 32(11):1331–1344. https://doi.org/10.1017/s1041610219002187

    Article  PubMed  Google Scholar 

  226. Albert PR (2018) Is poststroke depression the same as major depression? J Psychiatry Neurosci 43(2):76–78. https://doi.org/10.1503/jpn.180015

    Article  PubMed  PubMed Central  Google Scholar 

  227. Yan H, Fang M, Liu XY (2013) Role of microRNAs in stroke and poststroke depression. ScientificWorldJournal 2013:459692. https://doi.org/10.1155/2013/459692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Liang HB, He JR, Tu XQ, Ding KQ, Yang GY, Zhang Y, Zeng LL (2019) MicroRNA-140-5p: A novel circulating biomarker for early warning of late-onset post-stroke depression. J Psychiatr Res 115:129–141. https://doi.org/10.1016/j.jpsychires.2019.05.018

    Article  PubMed  Google Scholar 

  229. Panta A, Pandey S, Duncan IN, Duhamel S, Sohrabji F (2019) Mir363-3p attenuates post-stroke depressive-like behaviors in middle-aged female rats. Brain Behav Immun 78:31–40. https://doi.org/10.1016/j.bbi.2019.01.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, 215000, China

    Yutong Zhang, Hao Li, Qian Feng & Xingshun Xu

  2. Department of Neurology, Suzhou Yongding Hospital, Suzhou, 215028, China

    Yuehua Yang

  3. Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221600, China

    Wei Ge

  4. Institute of Neuroscience, Soochow University, Suzhou, 215123, China

    Xingshun Xu

  5. Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, China

    Xingshun Xu

Authors
  1. Yutong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuehua Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xingshun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZY and YY made the first draft. LH and FQ participated in the discussion of this manuscript and revised the part of this manuscript. XX and GW revised and finalized the paper. All authors read and approved the final manuscript. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Wei Ge or Xingshun Xu.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Yes.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yutong Zhang and Yuehua Yang are co-first authors.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Yang, Y., Li, H. et al. Investigating the Potential Mechanisms and Therapeutic Targets of Inflammatory Cytokines in Post-stroke Depression. Mol Neurobiol 61, 132–147 (2024). https://doi.org/10.1007/s12035-023-03563-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-023-03563-w

Keywords

Search

Navigation