Skip to main content

Advertisement

SpringerLink
Log in

Neuroinflammation Targeting Pyroptosis: Molecular Mechanisms and Therapeutic Perspectives in Stroke

  • Reviews
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Pyroptosis is a recently identified type of pro-inflammatory programmed cell death (PCD) mediated by inflammasomes and nucleotide oligomerization domain-like receptors (NLs) and dependent on members of the caspase family. Pyroptosis has been widely reported to participate in the occurrence and progression of various inflammatory diseases, including stroke, a frequently lethal disease with high prevalence and many complications. To date, there have been no effectively therapeutic strategies and methods for treating stroke. Pyroptosis is thought to be closely related to the occurrence and development of stroke. Understanding inflammatory responses induced by the activation of pyroptosis would be hopeful to provide feasible approaches and strategies. Targeting on molecules in the upstream or downstream of pyroptosis pathway has shown promise in the treatment of stroke. The present review summarizes current research on the characteristics of pyroptosis, the function and pathological phenomena of pyroptosis in stroke, the molecule mechanisms related to inflammatory pathways, and the drugs and other molecules that can affect outcomes after stroke. These findings may help identify possible targets or new strategies for the diagnosis and treatment of stroke.

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
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

Not applicable.

References

  1. Feigin VL (2019) Anthology of stroke epidemiology in the 20th and 21st centuries: assessing the past, the present, and envisioning the future. Int J Stroke 14:223–237

    Article  PubMed  Google Scholar 

  2. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L et al (2018) Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ 25:486–541

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zychlinsky A, Prevost MC, Sansonetti PJ (1992) Shigella flexneri induces apoptosis in infected macrophages. Nature 358:167–169

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Brennan MA, Cookson BT (2000) Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol 38:31–40

    Article  CAS  PubMed  Google Scholar 

  5. Fann DY, Lim YA, Cheng YL, Lok KZ, Chunduri P, Baik SH, Drummond GR, Dheen ST et al (2018) Evidence that NF-κB and MAPK signaling promotes NLRP inflammasome activation in neurons following ischemic stroke. Mol Neurobiol 55:1082–1096

    Article  CAS  PubMed  Google Scholar 

  6. Orning P, Weng D, Starheim K, Ratner D, Best Z, Lee B, Brooks A, Xia S et al (2018) Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science 362:1064–1069

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Platnich JM, Chung H, Lau A, Sandall CF, Bondzi-Simpson A, Chen HM, Komada T, Trotman-Grant AC et al (2018) Shiga toxin/lipopolysaccharide activates caspase-4 and gasdermin D to trigger mitochondrial reactive oxygen species upstream of the NLRP3 inflammasome. Cell Rep 25:1525-1536.e1527

    Article  CAS  PubMed  Google Scholar 

  8. Fu L, Zhang LM, Guan LN, Song YC, Zhang DX, Kang LQ, Liu FH (2023) Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia-reperfusion in rats. J Neuroimaging 33(5):742–751

  9. Li J, Hao JH, Yao D, Li R, Li XF, Yu ZY, Luo X, Liu XH, Wang MH, Wang W (2020) Caspase-1 inhibition prevents neuronal death by targeting the canonical inflammasome pathway of pyroptosis in a murine model of cerebral ischemia. CNS Neurosci Ther 26:925–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Poh L, Kang SW, Baik SH, Ng GYQ, She DT, Balaganapathy P, Dheen ST, Magnus T et al (2019) Evidence that NLRC4 inflammasome mediates apoptotic and pyroptotic microglial death following ischemic stroke. Brain Behav Immun 75:34–47

    Article  CAS  PubMed  Google Scholar 

  11. Cao Y, Zhang H, Lu X, Wang J, Zhang X, Sun S, Bao Z, Tian W et al (2020) Overexpression of MicroRNA-9a-5p ameliorates NLRP1 inflammasome-mediated ischemic injury in rats following ischemic stroke. Neuroscience 444:106–117

    Article  CAS  PubMed  Google Scholar 

  12. Li Q, Cao Y, Dang C, Han B, Han R, Ma H, Hao J, Wang L (2020) Inhibition of double-strand DNA-sensing cGAS ameliorates brain injury after ischemic stroke. EMBO Mol Med 12:e11002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fann DY, Lee SY, Manzanero S, Tang SC, Gelderblom M, Chunduri P, Bernreuther C, Glatzel M et al (2013) Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Dis 4:e790

    Article  CAS  PubMed  Google Scholar 

  14. Zhang L, Wang T, Chen XF, Xu ZX, Cao JB, Sun H (2021) TMEM59 protects against cerebral ischemic stroke by suppressing pyroptosis and microglial activation. Biochem Biophys Res Commun 543:72–79

    Article  CAS  PubMed  Google Scholar 

  15. Ma Q, Chen S, Hu Q, Feng H, Zhang JH, Tang J (2014) NLRP3 inflammasome contributes to inflammation after intracerebral hemorrhage. Ann Neurol 75:209–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yang X, Sun J, Kim TJ, Kim YJ, Ko SB, Kim CK, Jia X, Yoon BW (2018) Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage. Exp Neurol 310:22–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yang M, Deng S, Jiang J, Tian M, Xiao L, Gong Y (2023) Oxytocin improves intracerebral hemorrhage outcomes by suppressing neuronal pyroptosis and mitochondrial fission. Stroke 54:1888–1900

    Article  CAS  PubMed  Google Scholar 

  18. Ding Z, Zhong Z, Wang J, Zhang R, Shao J, Li Y, Wu G, Tu H et al (2022) Inhibition of dectin-1 alleviates neuroinflammatory injury by attenuating NLRP3 inflammasome-mediated pyroptosis after intracerebral hemorrhage in mice: preliminary study results. J Inflamm Res 15:5917–5933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jian D, Qin L, Gan H, Zheng S, Xiao H, Duan Y, Zhang M, Liang P (2023) NPAS4 exacerbates pyroptosis via transcriptionally regulating NLRP6 in the acute phase of intracerebral hemorrhage in mice. Int J Mol Sci 24:8320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lin X, Ye H, Siaw-Debrah F, Pan S, He Z, Ni H, Xu Z, Jin K (2018) AC-YVAD-CMK inhibits pyroptosis and improves functional outcome after intracerebral hemorrhage. Biomed Res Int 2018:3706047

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chen S, Zuo Y, Huang L, Sherchan P, Zhang J, Yu Z, Peng J, Zhang J et al (2019) The MC(4) receptor agonist RO27-3225 inhibits NLRP1-dependent neuronal pyroptosis via the ASK1/JNK/p38 MAPK pathway in a mouse model of intracerebral haemorrhage. Br J Pharmacol 176:1341–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Miao H, Jiang Y, Geng J, Zhang B, Zhu G, Tang J (2020) Edaravone administration confers neuroprotection after experimental intracerebral hemorrhage in rats via NLRP3 suppression. J Stroke Cerebrovasc Dis 29:104468

    Article  PubMed  Google Scholar 

  23. Zhang D, Yan H, Hu Y, Zhuang Z, Yu Z, Hang C (2015) Increased expression of NLRP3 inflammasome in wall of ruptured and unruptured human cerebral aneurysms: preliminary results. J Stroke Cerebrovasc Dis 24:972–979

    Article  PubMed  Google Scholar 

  24. Xu P, Hong Y, Xie Y, Yuan K, Li J, Sun R, Zhang X, Shi X et al (2021) TREM-1 exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental subarachnoid hemorrhage. Transl Stroke Res 12:643–659

    Article  CAS  PubMed  Google Scholar 

  25. Wu Q, Wang XL, Yu Q, Pan H, Zhang XS, Zhang QR, Wang HD, Zhang X (2016) Inflammasome proteins in cerebrospinal fluid of patients with subarachnoid hemorrhage are biomarkers of early brain injury and functional outcome. World Neurosurg 94:472–479

    Article  PubMed  Google Scholar 

  26. Yue T, Li X, Chen X, Zhu T, Li W, Wang B, Hang C (2023) Hemoglobin derived from subarachnoid hemorrhage-induced pyroptosis of neural stem cells via ROS/NLRP3/GSDMD pathway. Oxid Med Cell Longev 2023:4383332

    Article  PubMed  PubMed Central  Google Scholar 

  27. Fang Y, Wang X, Lu J, Shi H, Huang L, Shao A, Zhang A, Liu Y et al (2022) Inhibition of caspase-1-mediated inflammasome activation reduced blood coagulation in cerebrospinal fluid after subarachnoid haemorrhage. EBioMedicine 76:103843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Xu P, Tao C, Zhu Y, Wang G, Kong L, Li W, Li R, Li J et al (2021) TAK1 mediates neuronal pyroptosis in early brain injury after subarachnoid hemorrhage. J Neuroinflammation 18:188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chen J, Zhang C, Yan T, Yang L, Wang Y, Shi Z, Li M, Chen Q (2021) Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation. J Cell Physiol 236:6920–6931

    Article  CAS  PubMed  Google Scholar 

  30. Cai W, Wu Z, Lai J, Yao J, Zeng Y, Fang Z, Lin W, Chen J (2023) LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage. Front Immunol 14:1117310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wei B, Liu W, Jin L, Guo S, Fan H, Jin F, Wei C, Fang D et al (2022) Dexmedetomidine inhibits gasdermin D-induced pyroptosis via the PI3K/AKT/GSK3β pathway to attenuate neuroinflammation in early brain injury after subarachnoid hemorrhage in rats. Front Cell Neurosci 16:899484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. CristinadeBritoToscano E, LeandroMarcianoVieira É, BoniRochaDias B, VidigalCaliari M, PaulaGonçalves A, VarelaGiannetti A, MaurícioSiqueira J, KimieSuemoto C (2021) NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-β in sclerotic hippocampi. Brain Res 1752:147230

    Article  CAS  Google Scholar 

  33. Chivero ET, Thangaraj A, Tripathi A, Periyasamy P, Guo ML, Buch S (2021) NLRP3 inflammasome blockade reduces cocaine-induced microglial activation and neuroinflammation. Mol Neurobiol 58:2215–2230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yuan B, Zhou XM, You ZQ, Xu WD, Fan JM, Chen SJ, Han YL, Wu Q (2020) Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage. Cell Death Dis 11:76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lammert CR, Frost EL, Bellinger CE, Bolte AC, McKee CA, Hurt ME, Paysour MJ, Ennerfelt HE (2020) AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment. Nature 580:647–652

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yap JKY, Pickard BS, Chan EWL, Gan SY (2019) The role of neuronal NLRP1 inflammasome in Alzheimer’s disease: bringing neurons into the neuroinflammation game. Mol Neurobiol 56:7741–7753

    Article  CAS  PubMed  Google Scholar 

  37. Han C, Yang Y, Guan Q, Zhang X, Shen H, Sheng Y, Wang J, Zhou X et al (2020) New mechanism of nerve injury in Alzheimer’s disease: β-amyloid-induced neuronal pyroptosis. J Cell Mol Med 24:8078–8090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Barrington J, Lemarchand E, Allan SM (2017) A brain in flame; do inflammasomes and pyroptosis influence stroke pathology? Brain Pathol 27:205–212

    Article  PubMed  PubMed Central  Google Scholar 

  39. Clarke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA (2018) Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci USA 115:E1896-e1905

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gustin A, Kirchmeyer M, Koncina E, Felten P, Losciuto S, Heurtaux T, Tardivel A, Heuschling P (2015) NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes. Plos One 10:e0130624

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ebrahimi T, Rust M, Kaiser SN, Slowik A, Beyer C, Koczulla AR, Schulz JB, Habib P (2018) α1-antitrypsin mitigates NLRP3-inflammasome activation in amyloid β(1–42)-stimulated murine astrocytes. J Neuroinflammation 15:282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhong Y, Wang S, Yin Y, Yu J, Liu Y, Gao H (2023) Dexmedetomidine suppresses hippocampal astrocyte pyroptosis in cerebral hypoxic-ischemic neonatal rats by upregulating microRNA-148a-3p to inactivate the STAT/JMJD3 axis. Int Immunopharmacol 121:110440

    Article  CAS  PubMed  Google Scholar 

  43. Wang B, Lyu Z, Chan Y, Li Q, Zhang L, Liu K, Li Y, Yu Z (2021) Tongxinluo exerts inhibitory effects on pyroptosis and amyloid-β peptide accumulation after cerebral ischemia/reperfusion in rats. Evid Based Complement Alternat Med 2021:5788602

    ADS  PubMed  PubMed Central  Google Scholar 

  44. Walsh JG, Reinke SN, Mamik MK, McKenzie BA, Maingat F, Branton WG, Broadhurst DI, Power C (2014) Rapid inflammasome activation in microglia contributes to brain disease in HIV/AIDS. Retrovirology 11:35

    Article  PubMed  PubMed Central  Google Scholar 

  45. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9:857–865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. McKenzie BA, Mamik MK, Saito LB, Boghozian R, Monaco MC, Major EO, Lu JQ, Branton WG (2018) Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. Proc Natl Acad Sci USA 115:E6065-e6074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ji J, Xiang P, Li T, Lan L, Xu X, Lu G, Ji H, Zhang Y (2017) NOSH-NBP, a novel nitric oxide and hydrogen sulfide- releasing hybrid, attenuates ischemic stroke-induced neuroinflammatory injury by modulating microglia polarization. Front Cell Neurosci 11:154

    Article  PubMed  PubMed Central  Google Scholar 

  48. Ito M, Shichita T, Okada M, Komine R, Noguchi Y, Yoshimura A, Morita R (2015) Bruton’s tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury. Nat Commun 6:7360

    Article  ADS  PubMed  Google Scholar 

  49. Fann DY, Lee SY, Manzanero S, Chunduri P, Sobey CG, Arumugam TV (2013) Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev 12:941–966

    Article  CAS  PubMed  Google Scholar 

  50. Ma C, Liu S, Zhang S, Xu T, Yu X, Gao Y, Zhai C, Li C et al (2018) Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review). Int J Mol Med 42:2979–2990

    CAS  PubMed  Google Scholar 

  51. Li SJ, Zhang YF, Ma SH, Yi Y, Yu HY, Pei L, Feng D (2018) The role of NLRP3 inflammasome in stroke and central poststroke pain. Medicine 97:e11861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Pelegrin P (2021) P2X7 receptor and the NLRP3 inflammasome: partners in crime. Biochem Pharmacol 187:114385

    Article  CAS  PubMed  Google Scholar 

  53. DiVirgilio F, DalBen D, Sarti AC, Giuliani AL, Falzoni S (2017) The P2X7 receptor in infection and inflammation. Immunity 47:15–31

    Article  CAS  Google Scholar 

  54. Ye X, Shen T, Hu J, Zhang L, Zhang Y, Bao L, Cui C, Jin G et al (2017) Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse. Exp Neurol 292:46–55

    Article  CAS  PubMed  Google Scholar 

  55. Tan MS, Tan L, Jiang T, Zhu XC, Wang HF, Jia CD, Yu JT (2014) Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer’s disease. Cell Death Dis 5:e1382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rossol M, Pierer M, Raulien N, Quandt D, Meusch U, Rothe K, Schubert K, Schöneberg T et al (2012) Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors. Nat Commun 3:1329

    Article  ADS  PubMed  Google Scholar 

  57. Márta K, Hasan P, Rodríguez-Prados M, Paillard M, Hajnóczky G (2021) Pharmacological inhibition of the mitochondrial Ca(2+) uniporter: relevance for pathophysiology and human therapy. J Mol Cell Cardiol 151:135–144

    Article  PubMed  Google Scholar 

  58. Ishrat T, Mohamed IN, Pillai B, Soliman S, Fouda AY, Ergul A, El-Remessy AB, Fagan SC (2015) Thioredoxin-interacting protein: a novel target for neuroprotection in experimental thromboembolic stroke in mice. Mol Neurobiol 51:766–778

    Article  CAS  PubMed  Google Scholar 

  59. Ip WK, Medzhitov R (2015) Macrophages monitor tissue osmolarity and induce inflammatory response through NLRP3 and NLRC4 inflammasome activation. Nat Commun 6:6931

    Article  ADS  CAS  PubMed  Google Scholar 

  60. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225

    Article  ADS  CAS  PubMed  Google Scholar 

  61. Wang Y, Meng C, Zhang J, Wu J, Zhao J (2019) Inhibition of GSK-3β alleviates cerebral ischemia/reperfusion injury in rats by suppressing NLRP3 inflammasome activation through autophagy. Int Immunopharmacol 68:234–241

    Article  CAS  PubMed  Google Scholar 

  62. Coll RC, Hill JR, Day CJ, Zamoshnikova A, Boucher D, Massey NL, Chitty JL, Fraser JA et al (2019) MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nat Chem Biol 15:556–559

    Article  CAS  PubMed  Google Scholar 

  63. Bellut M, Bieber M, Kraft P, Weber ANR, Stoll G, Schuhmann MK (2023) Delayed NLRP3 inflammasome inhibition ameliorates subacute stroke progression in mice. J Neuroinflammation 20:4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jiang H, He H, Chen Y, Huang W, Cheng J, Ye J, Wang A, Tao J, Wang C, Liu Q et al (2017) Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J Exp Med 214:3219–3238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chen Y, He H, Lin B, Chen Y, Deng X, Jiang W, Zhou R (2021) RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor. Cell Mol Immunol 18:1425–1436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. González-Cofrade L, Green JP, Cuadrado I, Amesty Á, Oramas-Royo S, David B, Estévez-Braun A, Hortelano S et al (2023) Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors. Bioorg Chem 132:106362

    Article  PubMed  Google Scholar 

  67. An P, Xie J, Qiu S, Liu Y, Wang J, Xiu X, Li L, Tang M (2019) Hispidulin exhibits neuroprotective activities against cerebral ischemia reperfusion injury through suppressing NLRP3-mediated pyroptosis. Life Sci 232:116599

    Article  CAS  PubMed  Google Scholar 

  68. Cao X, Wang Y, Gao L (2021) CHRFAM7A Overexpression attenuates cerebral ischemia-reperfusion injury via inhibiting microglia pyroptosis mediated by the NLRP3/caspase-1 pathway. Inflammation 44:1023–1034

    Article  CAS  PubMed  Google Scholar 

  69. Hu J, Zeng C, Wei J, Duan F, Liu S, Zhao Y, Tan H (2020) The combination of Panax ginseng and Angelica sinensis alleviates ischemia brain injury by suppressing NLRP3 inflammasome activation and microglial pyroptosis. Phytomedicine 76:153251

    Article  CAS  PubMed  Google Scholar 

  70. Liang Q, Cai W, Zhao Y, Xu H, Tang H, Chen D, Qian F, Sun L (2020) Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis. Pharmacol Res 158:104884

    Article  CAS  PubMed  Google Scholar 

  71. Gu L, Sun M, Li R, Tao Y, Luo X, Xu J, Wu X, Xie Z (2022) Activation of RKIP binding ASC attenuates neuronal pyroptosis and brain injury via caspase-1/GSDMD signaling pathway after intracerebral hemorrhage in mice. Transl Stroke Res 13:1037–1054

    Article  CAS  PubMed  Google Scholar 

  72. Gu L, Sun M, Li R, Zhang X, Tao Y, Yuan Y, Luo X, Xie Z (2022) Didymin suppresses microglia pyroptosis and neuroinflammation through the Asc/caspase-1/GSDMD pathway following experimental intracerebral hemorrhage. Front Immunol 13:810582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Liang Y, Song P, Chen W, Xie X, Luo R, Su J, Zhu Y, Xu J et al (2020) Inhibition of caspase-1 ameliorates ischemia-associated blood-brain barrier dysfunction and integrity by suppressing pyroptosis activation. Front Cell Neurosci 14:540669

    Article  ADS  CAS  PubMed  Google Scholar 

  74. Suzuki H, Sozen T, Hasegawa Y, Chen W, Zhang JH (2009) Caspase-1 inhibitor prevents neurogenic pulmonary edema after subarachnoid hemorrhage in mice. Stroke 40:3872–3875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wu B, Ma Q, Khatibi N, Chen W, Sozen T, Cheng O, Tang J (2010) Ac-YVAD-CMK decreases blood-brain barrier degradation by inhibiting caspase-1 activation of interleukin-1β in intracerebral hemorrhage mouse model. Transl Stroke Res 1:57–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Zhao N, Zhuo X, Lu Y, Dong Y, Ahmed ME, Tucker D, Scott EL, Zhang Q (2017) Intranasal delivery of a caspase-1 inhibitor in the treatment of global cerebral ischemia. Mol Neurobiol 54:4936–4952

    Article  CAS  PubMed  Google Scholar 

  77. Ma Z, Li K, Chen P, Pan J, Li X, Zhao G (2020) Propofol attenuates inflammatory damage via inhibiting NLRP1-Casp1-Casp6 signaling in ischemic brain injury. Biol Pharm Bull 43:1481–1489

    Article  CAS  PubMed  Google Scholar 

  78. Li H, Guo Z, Chen J, Du Z, Lu H, Wang Z, Xi J, Bai Y (2022) Computational research of Belnacasan and new caspase-1 inhibitor on cerebral ischemia reperfusion injury. Aging 14:1848–1864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wang K, Sun Z, Ru J, Wang S, Huang L, Ruan L, Lin X, Jin K et al (2020) Ablation of GSDMD improves outcome of ischemic stroke through blocking canonical and non-canonical inflammasomes dependent pyroptosis in microglia. Front Neurol 11:577927

    Article  PubMed  PubMed Central  Google Scholar 

  80. Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X et al (2020) FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol 21:736–745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Rathkey JK, Zhao J, Liu Z, Chen Y, Yang J, Kondolf HC, Benson BL, Chirieleison SM et al (2018) Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci Immunol 3(26):eaat2738

  82. Humphries F, Shmuel-Galia L, Ketelut-Carneiro N, Li S, Wang B, Nemmara VV, Wilson R, Jiang Z et al (2020) Succination inactivates gasdermin D and blocks pyroptosis. Science 369:1633–1637

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yang J, Liu Z, Wang C, Yang R, Rathkey JK, Pinkard OW, Shi W, Chen Y et al (2018) Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. Proc Natl Acad Sci USA 115:6792–6797

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  84. Liu D, Dong Z, Xiang F, Liu H, Wang Y, Wang Q, Rao J (2020) Dendrobium alkaloids promote neural function after cerebral ischemia-reperfusion injury through inhibiting pyroptosis induced neuronal death in both in vivo and in vitro models. Neurochem Res 45:437–454

    Article  CAS  PubMed  Google Scholar 

  85. Zhang HS, Ouyang B, Ji XY, Liu MF (2021) Gastrodin alleviates cerebral ischaemia/reperfusion injury by inhibiting pyroptosis by regulating the lncRNA NEAT1/miR-22-3p Axis. Neurochem Res 46:1747–1758

    Article  CAS  PubMed  Google Scholar 

  86. Zhang Y, Wang H, Li H, Nan L, Xu W, Lin Y, Chu K (2021) Gualou Guizhi granule protects against OGD/R-induced injury by inhibiting cell pyroptosis via the PI3K/Akt signaling pathway. Evid Based Complement Alternat Med 2021:6613572

    PubMed  PubMed Central  Google Scholar 

  87. Ma DC, Zhang NN, Zhang YN, Chen HS (2021) Salvianolic acids for injection alleviates cerebral ischemia/reperfusion injury by switching M1/M2 phenotypes and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia in vivo and in vitro. J Ethnopharmacol 270:113776

    Article  CAS  PubMed  Google Scholar 

  88. She Y, Shao L, Zhang Y, Hao Y, Cai Y, Cheng Z, Deng C, Liu X (2019) Neuroprotective effect of glycosides in Buyang Huanwu Decoction on pyroptosis following cerebral ischemia-reperfusion injury in rats. J Ethnopharmacol 242:112051

    Article  CAS  PubMed  Google Scholar 

  89. Ran Y, Su W, Gao F, Ding Z, Yang S, Ye L, Chen X, Tian G (2021) Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia/macrophage pyroptosis through NF-κB suppression and NLRP3 inflammasome inhibition. Oxid Med Cell Longev 2021:1552127

    Article  PubMed  PubMed Central  Google Scholar 

  90. Wang M, Liu Z, Hu S, Duan X, Zhang Y, Peng C, Peng D, Han L (2020) Taohong Siwu Decoction ameliorates ischemic stroke injury via suppressing pyroptosis. Front Pharmacol 11:590453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wang K, Ru J, Zhang H, Chen J, Lin X, Lin Z, Wen M, Huang L et al (2020) Melatonin enhances the therapeutic effect of plasma exosomes against cerebral ischemia-induced pyroptosis through the TLR4/NF-κB pathway. Front Neurosci 14:848

    Article  PubMed  PubMed Central  Google Scholar 

  92. Zhu S, Zhang Z, Jia LQ, Zhan KX, Wang LJ, Song N, Liu Y, Cheng YY et al (2019) Valproic acid attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-pyroptosis pathways. Neurochem Int 124:141–151

    Article  CAS  PubMed  Google Scholar 

  93. Xia P, Pan Y, Zhang F, Wang N, Wang E, Guo Q, Ye Z (2018) Pioglitazone confers neuroprotection against ischemia-induced pyroptosis due to its inhibitory effects on HMGB-1/RAGE and Rac1/ROS pathway by activating PPAR-ɤ. Cell Physiol Biochem 45:2351–2368

    Article  CAS  PubMed  Google Scholar 

  94. Li F, Xu D, Hou K, Gou X, Lv N, Fang W, Li Y (2021) Pretreatment of indobufen and aspirin and their combinations with clopidogrel or ticagrelor alleviates inflammasome mediated pyroptosis via inhibiting NF-κB/NLRP3 pathway in ischemic stroke. J Neuroimmune Pharmacol 16:835–853

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the funding sources for supporting this work.

Funding

This work was supported by the University Student Innovative Training Program of Jining Medical University (cx2022001z) and the Natural Science Foundation of Shandong Province (ZR2020MH136, ZR2020QC079).

Author information

Authors and Affiliations

  1. Neurobiology Key Laboratory of Jining Medical University, Jining, 272067, China

    Xiwen Yuan, Yiwen Xia, Jing Chen & Chunmei Wang

  2. Institute of Clinical Pharmacy & Pharmacology, Jining First People’s Hospital, Jining Medical University, Jining, 272011, China

    Pei Jiang

  3. Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK

    Jing Chen

Authors
  1. Xiwen Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yiwen Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chunmei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jing Chen or Chunmei Wang.

Ethics declarations

Ethical approval

The study was approved by the local ethics board of Jining Medical University (JNMC-2023-DW-032) and met the standards of the Guide for the Care and Use of Laboratory Animals issued by the Ministry of Science and Technology of the People’s Republic of China in 2006.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

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.

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

Yuan, X., Xia, Y., Jiang, P. et al. Neuroinflammation Targeting Pyroptosis: Molecular Mechanisms and Therapeutic Perspectives in Stroke. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04050-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-024-04050-6

Keywords

Search

Navigation