Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Microglial STING activation promotes neuroinflammation and pathological changes in experimental mice with intracerebral haemorrhage

Acta Pharmacologica Sinica volume 46, pages 2376–2392 (2025)Cite this article

Abstract

Neuroinflammation, a significant contributor to secondary brain injury, plays a critical role in the pathological process and prognosis of intracerebral haemorrhage (ICH). Thus, developing interventions to mitigate secondary neuroimmune deterioration is of paramount importance. Currently, no effective immunomodulatory drugs are available for ICH. The cyclic GMP-AMP synthase (cGAS)−stimulator of interferon genes (STING) pathway is a recently identified innate immune-sensing pathway primarily expressed in microglia within the central nervous system (CNS) that has been implicated in the pathophysiology of various neurological diseases. In this study we investigated the role of cGAS-STING pathway in ICH. A collagenase model of ICH was established in mice. Brain tissues were collected on D1 or D3 post-ICH. We observed a significant increase in double-stranded (dsDNA) levels and activation of the cGAS-STING pathway in the perihaematomal region of ICH mice. Administration of a blood brain barrier-permeable STING antagonist H151 (10 mg/kg, i.p.) significantly decreased cell apoptosis, alleviated hematoma growth, and improved motor impairments in ICH mice, accompanied by inhibiting the STING pathway in microglia, reducing production/release of the cGAS-STING pathway downstream inflammatory factors, NLRP3 inflammasome activation and gasdermin D (GSDMD)-induced microglial pyroptosis. Microglial Sting conditional knockout significantly mitigated ICH-induced neuroinflammatory responses, pathological damage and motor dysfunction. These results suggest that the microglial STING pathway promotes brain pathological damage and behavioural defects in ICH mice by activating the NLRP3 inflammasome and microglial pyroptosis. The STING pathway may serve as a potential therapeutic target for ICH-induced secondary brain injury.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Accumulation of dsDNA and upregulation of the cGAS‒STING pathway in the perihaematomal region of ICH mice.
Fig. 2: Increased expression of NLRP3, GSDMD, and GSDMD-N and colocalization of GSDMD with microglia in the perihaematomal region following ICH.
Fig. 3: H151 administration inhibits STING pathway activation and inflammatory factor production following ICH.
Fig. 4: Administration of H151 attenuates NLRP3 inflammasome activation and microglial pyroptosis following ICH.
Fig. 5: Administration of H151 reduces ROS levels and TXNIP expression in the perihaematomal region of ICH mice.
Fig. 6: Administration of H151 mitigated neuronal damage, intracerebral haemorrhage, and motor function deficits in ICH mice.
Fig. 7: Microglial Sting knockout inhibits STING pathway activation and inflammatory factor production following ICH.
Fig. 8: Microglial Sting knockout reduces NLRP3 inflammasome activation and microglial pyroptosis following ICH.
Fig. 9: Microglial Sting deletion mitigates neuronal damage, intracerebral haemorrhage, and motor function impairments following ICH.

Similar content being viewed by others

References

  1. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5:53–63.

    Article  PubMed  Google Scholar 

  2. Broderick JP, Grotta JC, Naidech AM, Steiner T, Sprigg N, Toyoda K, et al. The story of intracerebral hemorrhage: from recalcitrant to treatable disease. Stroke. 2021;52:1905–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral haemorrhage: current approaches to acute management. Lancet. 2018;392:1257–68.

    Article  PubMed  Google Scholar 

  4. Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA, Wolfe SQ. Neuroinflammation after intracerebral hemorrhage and potential therapeutic targets. J Stroke. 2020;22:29–46.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Magid-Bernstein J, Girard R, Polster S, Srinath A, Romanos S, Awad IA, et al. Cerebral hemorrhage: pathophysiology, treatment, and future directions. Circ Res. 2022;130:1204–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lan X, Han X, Li Q, Yang QW, Wang J. Modulators of microglial activation and polarization after intracerebral haemorrhage. Nat Rev Neurol. 2017;13:420–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shao A, Zhu Z, Li L, Zhang S, Zhang J. Emerging therapeutic targets associated with the immune system in patients with intracerebral haemorrhage (ICH): from mechanisms to translation. EBioMedicine. 2019;45:615–23.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Heneka MT, McManus RM, Latz E. Inflammasome signalling in brain function and neurodegenerative disease. Nat Rev Neurosci. 2018;19:610–21.

    Article  CAS  PubMed  Google Scholar 

  9. Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19:477–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen D, Dixon BJ, Doycheva DM, Li B, Zhang Y, Hu Q, et al. IRE1alpha inhibition decreased TXNIP/NLRP3 inflammasome activation through miR-17-5p after neonatal hypoxic-ischemic brain injury in rats. J Neuroinflamm. 2018;15:32.

    Article  Google Scholar 

  11. Li W, Shen N, Kong L, Huang H, Wang X, Zhang Y, et al. STING mediates microglial pyroptosis via interaction with NLRP3 in cerebral ischaemic stroke. Stroke Vasc Neurol. 2024;9:153–64.

    Article  PubMed  Google Scholar 

  12. Lei P, Li Z, Hua Q, Song P, Gao L, Zhou L, et al. Ursolic acid alleviates neuroinflammation after intracerebral hemorrhage by mediating microglial pyroptosis via the NF-kappaB/NLRP3/GSDMD pathway. Int J Mol Sci. 2023;24:14771.

  13. Toldo S, Abbate A. The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases. Nat Rev Cardiol. 2024;21:219–37.

    Article  CAS  PubMed  Google Scholar 

  14. Guo S, Wang R, Hu J, Sun L, Zhao X, Zhao Y, et al. Photobiomodulation promotes hippocampal CA1 NSC differentiation toward neurons and facilitates cognitive function recovery involving NLRP3 inflammasome mitigation following global cerebral ischemia. Front Cell Neurosci. 2021;15:731855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 2021;6:128.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wei C, Jiang W, Wang R, Zhong H, He H, Gao X, et al. Brain endothelial GSDMD activation mediates inflammatory BBB breakdown. Nature. 2024;629:893–900.

    Article  CAS  PubMed  Google Scholar 

  17. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016;535:153–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339:826–30.

    Article  CAS  PubMed  Google Scholar 

  19. Gulen MF, Samson N, Keller A, Schwabenland M, Liu C, Gluck S, et al. cGAS-STING drives ageing-related inflammation and neurodegeneration. Nature. 2023;620:374–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhang X, Bai XC, Chen ZJ. Structures and mechanisms in the cGAS-STING innate immunity pathway. Immunity. 2020;53:43–53.

    Article  CAS  PubMed  Google Scholar 

  21. Balka KR, Louis C, Saunders TL, Smith AM, Calleja DJ, D’Silva DB, et al. TBK1 and IKKepsilon act redundantly to mediate STING-Induced NF-kappaB responses in myeloid cells. Cell Rep. 2020;31:107492.

    Article  CAS  PubMed  Google Scholar 

  22. Ding R, Li H, Liu Y, Ou W, Zhang X, Chai H, et al. Activating cGAS-STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis. J Neuroinflamm. 2022;19:137.

    Article  CAS  Google Scholar 

  23. Li Y, Li J, Yu Q, Ji L, Peng B. METTL14 regulates microglia/macrophage polarization and NLRP3 inflammasome activation after ischemic stroke by the KAT3B-STING axis. Neurobiol Dis. 2023;185:106253.

    Article  CAS  PubMed  Google Scholar 

  24. Gaidt MM, Ebert TS, Chauhan D, Ramshorn K, Pinci F, Zuber S, et al. The DNA inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3. Cell. 2017;171:1110–24.e18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang W, Hu D, Wu C, Feng Y, Li A, Liu W, et al. STING promotes NLRP3 localization in ER and facilitates NLRP3 deubiquitination to activate the inflammasome upon HSV-1 infection. PLoS Pathog. 2020;16:e1008335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gamdzyk M, Doycheva DM, Araujo C, Ocak U, Luo Y, Tang J, et al. cGAS/STING pathway activation contributes to delayed neurodegeneration in neonatal hypoxia-ischemia rat model: possible involvement of LINE-1. Mol Neurobiol. 2020;57:2600–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shao J, Meng Y, Yuan K, Wu Q, Zhu S, Li Y, et al. RU.521 mitigates subarachnoid hemorrhage-induced brain injury via regulating microglial polarization and neuroinflammation mediated by the cGAS/STING/NF-kappaB pathway. Cell Commun Signal. 2023;21:264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Xu C, Pan Y, Zhang H, Sun Y, Cao Y, Qi P, et al. Platelet-membrane-coated polydopamine nanoparticles for neuroprotection by reducing oxidative stress and repairing damaged vessels in intracerebral hemorrhage. Adv Health Mater. 2023;12:e2300797.

    Article  Google Scholar 

  29. Kobritz M, Borjas T, Patel V, Coppa G, Aziz M, Wang P. H151, a small molecule inhibitor of sting as a novel therapeutic in intestinal ischemia-reperfusion injury. Shock. 2022;58:241–50.

    Article  CAS  PubMed  Google Scholar 

  30. Xu C, Jiang F, Mao Y, Wei W, Song J, Jia F, et al. Disulfiram attenuates cell and tissue damage and blood‒brain barrier dysfunction after intracranial haemorrhage by inhibiting the classical pyroptosis pathway. Sci Rep. 2024;14:21860.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ren H, Kong Y, Liu Z, Zang D, Yang X, Wood K, et al. Selective NLRP3 (pyrin domain-containing protein 3) inflammasome inhibitor reduces brain injury after intracerebral hemorrhage. Stroke. 2018;49:184–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Fan H, Ding R, Liu W, Zhang X, Li R, Wei B, et al. Heat shock protein 22 modulates NRF1/TFAM-dependent mitochondrial biogenesis and DRP1-sparked mitochondrial apoptosis through AMPK-PGC1alpha signaling pathway to alleviate the early brain injury of subarachnoid hemorrhage in rats. Redox Biol. 2021;40:101856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yang J, Li Q, Wang Z, Qi C, Han X, Lan X, et al. Multimodality MRI assessment of grey and white matter injury and blood-brain barrier disruption after intracerebral haemorrhage in mice. Sci Rep. 2017;7:40358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu Y, Cui F, Xu A, Wang B, Ma Y, Zhang Q, et al. Interaction between the PERK/ATF4 branch of the endoplasmic reticulum stress and mitochondrial one-carbon metabolism regulates neuronal survival after intracerebral hemorrhage. Int J Biol Sci. 2024;20:4277–96.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Xu J, Chen Z, Yu F, Liu H, Ma C, Xie D, et al. IL-4/STAT6 signaling facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice. Proc Natl Acad Sci USA. 2020;117:32679–90.

  36. Xiao Y, Zhao C, Tai Y, Li B, Lan T, Lai E, et al. STING mediates hepatocyte pyroptosis in liver fibrosis by epigenetically activating the NLRP3 inflammasome. Redox Biol. 2023;62:102691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Haag SM, Gulen MF, Reymond L, Gibelin A, Abrami L, Decout A, et al. Targeting STING with covalent small-molecule inhibitors. Nature. 2018;559:269–73.

    Article  CAS  PubMed  Google Scholar 

  38. Wu C, Zhang S, Sun H, Li A, Hou F, Qi L, et al. STING inhibition suppresses microglia-mediated synapses engulfment and alleviates motor functional deficits after stroke. J Neuroinflamm. 2024;21:86.

    Article  CAS  Google Scholar 

  39. Xie X, Ma G, Li X, Zhao J, Zhao Z, Zeng J. Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5xFAD mice. Nat Aging. 2023;3:202–12.

    Article  CAS  PubMed  Google Scholar 

  40. Li Y, Liu C, Wang G, Wang H, Liu X, Huang C, et al. HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPARgamma/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice. Neuropharmacology. 2023;237:109633.

    Article  CAS  PubMed  Google Scholar 

  41. Karmakar M, Minns M, Greenberg EN, Diaz-Aponte J, Pestonjamasp K, Johnson JL, et al. N-GSDMD trafficking to neutrophil organelles facilitates IL-1beta release independently of plasma membrane pores and pyroptosis. Nat Commun. 2020;11:2212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hayman TJ, Baro M, MacNeil T, Phoomak C, Aung TN, Cui W, et al. STING enhances cell death through regulation of reactive oxygen species and DNA damage. Nat Commun. 2021;12:2327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li N, Zhou H, Wu H, Wu Q, Duan M, Deng W, et al. STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol. 2019;24:101215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang C, Yang T, Xiao J, Xu C, Alippe Y, Sun K, et al. NLRP3 inflammasome activation triggers gasdermin D-independent inflammation. Sci Immunol. 2021;6:eabj3859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Coll RC, Robertson AA, Chae JJ, Higgins SC, Munoz-Planillo R, Inserra MC, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015;21:248–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tapia-Abellan A, Angosto-Bazarra D, Martinez-Banaclocha H, de Torre-Minguela C, Ceron-Carrasco JP, Perez-Sanchez H, et al. MCC950 closes the active conformation of NLRP3 to an inactive state. Nat Chem Biol. 2019;15:560–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y, Zhao J, et al. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol. 2020;21:736–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Aglietti RA, Estevez A, Gupta A, Ramirez MG, Liu PS, Kayagaki N, et al. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. Proc Natl Acad Sci USA. 2016;113:7858–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535:111–6.

    Article  CAS  PubMed  Google Scholar 

  50. Devant P, Kagan JC. Molecular mechanisms of gasdermin D pore-forming activity. Nat Immunol. 2023;24:1064–75.

    Article  CAS  PubMed  Google Scholar 

  51. Zhao Q, Wei Y, Pandol SJ, Li L, Habtezion A. STING signaling promotes inflammation in experimental acute pancreatitis. Gastroenterology. 2018;154:1822–35 e2.

    Article  CAS  PubMed  Google Scholar 

  52. Abdullah A, Zhang M, Frugier T, Bedoui S, Taylor JM, Crack PJ. STING-mediated type-I interferons contribute to the neuroinflammatory process and detrimental effects following traumatic brain injury. J Neuroinflamm. 2018;15:323.

    Article  CAS  Google Scholar 

  53. Woo MS, Mayer C, Binkle-Ladisch L, Sonner JK, Rosenkranz SC, Shaposhnykov A, et al. STING orchestrates the neuronal inflammatory stress response in multiple sclerosis. Cell. 2024;187:4043–60.e30.

    Article  CAS  PubMed  Google Scholar 

  54. Hou Y, Wei Y, Lautrup S, Yang B, Wang Y, Cordonnier S, et al. NAD+ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer’s disease via cGAS-STING. Proc Natl Acad Sci USA. 2021;118:e2011226118.

  55. Hinkle JT, Patel J, Panicker N, Karuppagounder SS, Biswas D, Belingon B, et al. STING mediates neurodegeneration and neuroinflammation in nigrostriatal alpha-synucleinopathy. Proc Natl Acad Sci USA. 2022;119:e2118819119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhou X, Wang J, Yu L, Qiao G, Qin D, Yuen-Kwan Law B, et al. Mitophagy and cGAS-STING crosstalk in neuroinflammation. Acta Pharm Sin B. 2024;14:3327–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Maimaiti M, Li C, Cheng M, Zhong Z, Hu J, Yang L, et al. Blocking cGAS-STING pathway promotes post-stroke functional recovery in an extended treatment window via facilitating remyelination. Med. 2024;5:622–44.e8.

    Article  CAS  PubMed  Google Scholar 

  58. Li Q, Cao Y, Dang C, Han B, Han R, Ma H, et al. Inhibition of double-strand DNA-sensing cGAS ameliorates brain injury after ischemic stroke. EMBO Mol Med. 2020;12:e11002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bader ER, Pana TA, Barlas RS, Metcalf AK, Potter JF, Myint PK. Elevated inflammatory biomarkers and poor outcomes in intracerebral hemorrhage. J Neurol. 2022;269:6330–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gu T, Pan J, Chen L, Li K, Wang L, Zou Z, et al. Association of inflammatory cytokines expression in cerebrospinal fluid with the severity and prognosis of spontaneous intracerebral hemorrhage. BMC Neurol. 2024;24:7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Xue M, Yong VW. Neuroinflammation in intracerebral haemorrhage: immunotherapies with potential for translation. Lancet Neurol. 2020;19:1023–32.

    Article  CAS  PubMed  Google Scholar 

  62. Pan Y, You Y, Sun L, Sui Q, Liu L, Yuan H, et al. The STING antagonist H-151 ameliorates psoriasis via suppression of STING/NF-kappaB-mediated inflammation. Br J Pharmacol. 2021;178:4907–22.

    Article  CAS  PubMed  Google Scholar 

  63. Wu B, Xu MM, Fan C, Feng CL, Lu QK, Lu HM, et al. STING inhibitor ameliorates LPS-induced ALI by preventing vascular endothelial cells-mediated immune cells chemotaxis and adhesion. Acta Pharmacol Sin. 2022;43:2055–66.

    Article  CAS  PubMed  Google Scholar 

  64. Hu Z, Zhang F, Brenner M, Jacob A, Wang P. The protective effect of H151, a novel STING inhibitor, in renal ischemia-reperfusion-induced acute kidney injury. Am J Physiol Ren Physiol. 2023;324:F558–F67.

    Article  CAS  Google Scholar 

  65. Qiao H, Chiu Y, Liang X, Xia S, Ayrapetyan M, Liu S, et al. Microglia innate immune response contributes to the antiviral defense and blood-CSF barrier function in human choroid plexus organoids during HSV-1 infection. J Med Virol. 2023;95:e28472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zamiri K, Kesari S, Paul K, Hwang SH, Hammock B, Kaczor-Urbanowicz KE, et al. Therapy of autoimmune inflammation in sporadic amyotrophic lateral sclerosis: dimethyl fumarate and H-151 downregulate inflammatory cytokines in the cGAS-STING pathway. FASEB J. 2023;37:e23068.

    Article  CAS  PubMed  Google Scholar 

  67. Ohashi SN, DeLong JH, Kozberg MG, Mazur-Hart DJ, van Veluw SJ, Alkayed NJ, et al. Role of inflammatory processes in hemorrhagic stroke. Stroke. 2023;54:605–19.

    Article  PubMed  Google Scholar 

  68. Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339:786–91.

    Article  CAS  PubMed  Google Scholar 

  69. Loan JJ, Kirby C, Emelianova K, Dando OR, Poon MT, Pimenova L, et al. Secondary injury and inflammation after intracerebral haemorrhage: a systematic review and meta-analysis of molecular markers in patient brain tissue. J Neurol Neurosurg Psychiatry. 2022;93:126–32.

    Article  PubMed  Google Scholar 

  70. Gu F, Wang Z, Ding H, Tao X, Zhang J, Dai K, et al. Microglial mitochondrial DNA release contributes to neuroinflammation after intracerebral hemorrhage through activating AIM2 inflammasome. Exp Neurol. 2024;382:114950.

    Article  CAS  PubMed  Google Scholar 

  71. Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, et al. TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS. Cell. 2020;183:636–49.e18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was funded by the National Key R&D Program of China (2022YFF1203005), the China National Science and Technology Innovation 2030 (2021ZD0204004), the National Natural Science Foundation of China (grant number 22177068, 22494694, 82171292), and the Natural Science Foundation of Shanghai (Grant 24ZR1491100, 22ZR1434700).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, China

    Yu-xiao Xue, Yu-hao Sun & Liu-guan Bian

  2. Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China

    Yu-xiao Xue, Yi-jun Chen, Mei-zhen Qin, Fan-fan Shang, Yi-ting Lu, Ao Zhang, Yang Yu & Chun-yong Ding

Authors
  1. Yu-xiao Xue
    View author publications

    Search author on:PubMed Google Scholar

  2. Yi-jun Chen
    View author publications

    Search author on:PubMed Google Scholar

  3. Mei-zhen Qin
    View author publications

    Search author on:PubMed Google Scholar

  4. Fan-fan Shang
    View author publications

    Search author on:PubMed Google Scholar

  5. Yi-ting Lu
    View author publications

    Search author on:PubMed Google Scholar

  6. Yu-hao Sun
    View author publications

    Search author on:PubMed Google Scholar

  7. Liu-guan Bian
    View author publications

    Search author on:PubMed Google Scholar

  8. Ao Zhang
    View author publications

    Search author on:PubMed Google Scholar

  9. Yang Yu
    View author publications

    Search author on:PubMed Google Scholar

  10. Chun-yong Ding
    View author publications

    Search author on:PubMed Google Scholar

Contributions

YXX, YJC, MZQ, and FFS performed the experiments. YXX processed and analysed the data. YXX, YY, and CYD wrote the manuscript. YHS, AZ, LGB, YTL, and YY provided the critical reagents and participated in the discussions. CYD, YY, and AZ conceived and designed the study. All the authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Liu-guan Bian, Ao Zhang, Yang Yu or Chun-yong Ding.

Ethics declarations

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.

Supplementary information

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

Xue, Yx., Chen, Yj., Qin, Mz. et al. Microglial STING activation promotes neuroinflammation and pathological changes in experimental mice with intracerebral haemorrhage. Acta Pharmacol Sin 46, 2376–2392 (2025). https://doi.org/10.1038/s41401-025-01540-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41401-025-01540-8

Keywords

This article is cited by

Search

Advanced search

Quick links