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The SAH rat model was established by performing intravascular puncture, followed by the administration of Hirudin and Nod-like receptor protein 3 (NLRP3) agonist Nigericin into the lateral ventricle. The SAH grading, neurological score, brain water content, blood-brain barrier (BBB) permeability, neuronal damage, inflammatory reaction, neuronal death, distribution of microglia marker Iba-1 and expression levels of NLRP3 inflammasomal-related proteins were evaluated at 72 h post-SAH. Hirudin treatment significantly ameliorated neurological scores and attenuated brain edema, BBB permeability, inflammatory response, microglia activation, and pyroptosis in SAH rats. Additionally, Hirudin treatment downregulated the expression levels of NLRP3 inflammasomal- related proteins, such as NLRP3, apoptosis- associated speck-like protein (ASC) and cleaved caspsase-1. However, Nigericin partially counteracted the aforementioned effects of Hirudin, indicating that Hirudin exerted its inhibitory effect on pyroptosis by modulating the NLRP3 inflammasome pathway. The neuroprotective effect of Hirudin on EBI following SAH is attributed its ability to inhibit pyroptosis mediated by NLRP3 inflammasome, suggesting its potential as a promising therapeutic approach for SAH.<\/jats:p>","DOI":"10.33549\/physiolres.935454","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T05:57:51Z","timestamp":1747720671000},"page":"301-312","source":"Crossref","is-referenced-by-count":2,"title":["Hirudin Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats via Regulating NLRP3 Inflammasome-Mediated Pyroptosis"],"prefix":"10.33549","author":[{"given":"M","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Luo","sequence":"additional","affiliation":[{"name":"Zhuang Medicine Classic Ward, Guangxi International Zhuang Medicine Hospital, Nanning, China. 18500199871@163.com"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8:355-369. https:\/\/doi.org\/10.1016\/S1474-4422(09)70025-0","DOI":"10.1016\/s1474-4422(09)70025-0"},{"key":"ref1","unstructured":"Rabinstein AA. Subarachnoid hemorrhage. Neurology. 2013;80:e56-59. https:\/\/doi.org\/10.1212\/ WNL.0b013e3182834b22"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Dority JS, Oldham JS. Subarachnoid Hemorrhage: An Update. Anesthesiol Clin. 2016;34:577-600. https:\/\/doi.org\/10.1016\/j.anclin.2016.04.009","DOI":"10.1016\/j.anclin.2016.04.009"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Persson HC, Carlsson L, Sunnerhagen KS. Life situation 5 years after subarachnoid haemorrhage. Acta Neurol Scand. 2018;137:99-104. https:\/\/doi.org\/10.1111\/ane.12815","DOI":"10.1111\/ane.12815"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Korja M, Lehto H, Juvela S, Kaprio J. Incidence of subarachnoid hemorrhage is decreasing together with decreasing smoking rates. Neurology. 2016;87:1118-1123. https:\/\/doi.org\/10.1212\/WNL.0000000000003091","DOI":"10.1212\/wnl.0000000000003091"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10:44-58. https:\/\/doi.org\/10.1038\/nrneurol.2013.246","DOI":"10.1038\/nrneurol.2013.246"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Rass V, Helbok R. Early brain injury after poor-grade subarachnoid hemorrhage. Curr Neurol Neurosci Rep. 2019;19:78. https:\/\/doi.org\/10.1007\/s11910-019-0990-3","DOI":"10.1007\/s11910-019-0990-3"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Lauzier DC, Jayaraman K. Early brain injury after subarachnoid hemorrhage: incidence and mechanisms. stroke. 2023;54:1426-1440. https:\/\/doi.org\/10.1161\/STROKEAHA.122.040072","DOI":"10.1161\/strokeaha.122.040072"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Li R, Liu W, Yin J, Chen Y, Guo S, Fan H, Li X, Zhang X, He X, Duan C. TSG-6 attenuates inflammation-induced brain injury via modulation of microglial polarization in SAH rats through the SOCS3\/STAT3 pathway. J Neuroinflammation. 2018;15:231. https:\/\/doi.org\/10.1186\/s12974-018-1279-1","DOI":"10.1186\/s12974-018-1279-1"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Cao C, Ding J, Cao D, Li B, Wu J, Li X, Li H, Cui G, Shen H, Chen G. TREM2 modulates neuroinflammation with elevated IRAK3 expression and plays a neuroprotective role after experimental SAH in rats. Neurobiol Dis. 2022;171:105809. https:\/\/doi.org\/10.1016\/j.nbd.2022.105809","DOI":"10.1016\/j.nbd.2022.105809"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Li T, Zhang Y, Lu Q, Lei L, Du J, Lu X. GPNMB Ameliorates Neuroinflammation Via the Modulation of AMPK\/NF\u03baB Signaling Pathway After SAH in Mice. J Neuroimmune Pharmacol. 2023;18:628-639. https:\/\/doi.org\/10.1007\/s11481-023-10087-6","DOI":"10.21203\/rs.3.rs-2488443\/v1"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Boise LH, Collins CM. Salmonella-induced cell death: apoptosis, necrosis or programmed cell death? Trends Microbiol. 2001;9:64-67. https:\/\/doi.org\/10.1016\/S0966-842X(00)01937-5","DOI":"10.1016\/s0966-842x(00)01937-5"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001;9:113-114. https:\/\/doi.org\/10.1016\/S0966-842X(00)01936-3","DOI":"10.1016\/s0966-842x(00)01936-3"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Xu P, Li F, Tang H. Pyroptosis and airway homeostasis regulation. Physiol Res. 2023;72:1-13. https:\/\/doi.org\/10.33549\/physiolres.934971","DOI":"10.33549\/physiolres.934971"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Fink SL, Cookson BT. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol. 2006;8:1812-1825. https:\/\/doi.org\/10.1111\/j.1462-5822.2006.00751.x","DOI":"10.1111\/j.1462-5822.2006.00751.x"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Fink SL, Cookson BT. Pyroptosis and host cell death responses during Salmonella infection. 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Exp Ther Med. 2021;22:1391. https:\/\/doi.org\/10.3892\/etm.2021.10827","DOI":"10.3892\/etm.2021.10827"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Liu C, Yao K, Tian Q, Guo Y, Wang G, He P, Wang J, Wang J, Zhang Z, Li M. CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-\u03baB pathway. Redox Biol. 2023;68:102960. https:\/\/doi.org\/10.1016\/j.redox.2023.102960","DOI":"10.1016\/j.redox.2023.102960"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Junren C, Xiaofang X, Huiqiong Z, Gangmin L, Yanpeng Y, Xiaoyu C, Yuqing G, Yanan L, Yue Z, Fu P, Cheng P. Pharmacological activities and mechanisms of hirudin and its derivatives - a review. Front Pharmacol. 2021;12:660757. https:\/\/doi.org\/10.3389\/fphar.2021.660757","DOI":"10.3389\/fphar.2021.660757"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Li WQ, Qin ZS, Chen S, Cheng D, Yang SC, Choi YMM, Chu B, Zhou WH, Zhang ZJ. Hirudin alleviates acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation: In vivo and in vitro approaches. Int Immunopharmacol. 2022;110:108967. https:\/\/doi.org\/10.1016\/j.intimp.2022.108967","DOI":"10.1016\/j.intimp.2022.108967"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Sun Z, Zhao Z, Zhao S, Sheng Y, Zhao Z, Gao C, Li J, Liu X. Recombinant hirudin treatment modulates aquaporin-4 and aquaporin-9 expression after intracerebral hemorrhage in vivo. Mol Biol Rep. 2009;36:1119-1127. https:\/\/doi.org\/10.1007\/s11033-008-9287-3","DOI":"10.1007\/s11033-008-9287-3"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Xia X, Li M, Wei R, Li J, Lei Y, Zhang M. Intracerebral hirudin injection alleviates cognitive impairment and oxidative stress and promotes hippocampal neurogenesis in rats subjected to cerebral ischemia. Neuropathology. 2023;43:362-372. https:\/\/doi.org\/10.1111\/neup.12897","DOI":"10.1111\/neup.12897"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Luo G, Chen L, Chen M, Mao L, Zeng Q, Zou Y, Xue J, Liu P, Wu Q, Yang S, Liu M. Hirudin inhibit the formation of NLRP3 inflammasome in cardiomyocytes via suppressing oxidative stress and activating mitophagy. Heliyon. 2024;10:e23077. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e23077","DOI":"10.1016\/j.heliyon.2023.e23077"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Bai Y, Bai J, Lu P, Jing YM, Zheng WC, Wang LY, Wang JH, Wang F. Hirudin ameliorates myocardial ischemia-reperfusion injury in a rat model of hemorrhagic shock and resuscitation: roles of NLRP3-signaling pathway. Mol Cell Biochem. 2024;479:63-72. https:\/\/doi.org\/10.1007\/s11010-023-04717-z","DOI":"10.1007\/s11010-023-04717-z"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Sugawara T, Ayer R, Jadhav V, Zhang JH. A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. J Neurosci Methods. 2008;167:327-334. https:\/\/doi.org\/10.1016\/j.jneumeth.2007.08.004","DOI":"10.1016\/j.jneumeth.2007.08.004"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Karabiyikoglu M, Hua Y, Keep RF, Ennis SR, Xi G. Intracerebral hirudin injection attenuates ischemic damage and neurologic deficits without altering local cerebral blood flow. J Cereb Blood Flow Metab. 2004;24:159-166. https:\/\/doi.org\/10.1097\/01.WCB.0000100062.36077.84","DOI":"10.1097\/01.wcb.0000100062.36077.84"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Zhang D, Yan H, Li H, Hao S, Zhuang Z, Liu M, Sun Q, Yang Y, Zhou M, Li K, Hang C. TGF\u03b2-activated Kinase 1 (TAK1) Inhibition by 5Z-7-oxozeaenol attenuates early brain injury after experimental subarachnoid hemorrhage. J Biol Chem. 2015;290:19900-19909. https:\/\/doi.org\/10.1074\/jbc.M115.636795","DOI":"10.1074\/jbc.m115.636795"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Cai W, Wu Z, Lai J, Yao J, Zeng Y, Fang Z, Lin W, Chen J, Xu C, Chen X. LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage. Front Immunol. 2023;14:1117310. https:\/\/doi.org\/10.3389\/fimmu.2023.1117310","DOI":"10.3389\/fimmu.2023.1117310"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Garcia JH, Wagner S, Liu KF, Hu XJ. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke. 1995;26:627-634; discussion 635. https:\/\/doi.org\/10.1161\/01.STR.26.4.627","DOI":"10.1161\/01.str.26.4.627"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Pan P, Zhang X, Li Q, Zhao H, Qu J, Zhang JH, Liu X, Feng H, Chen Y. Cyclosporine A alleviated matrix metalloproteinase 9 associated blood-brain barrier disruption after subarachnoid hemorrhage in mice. Neurosci Lett. 2017;649:7-13. https:\/\/doi.org\/10.1016\/j.neulet.2017.03.050","DOI":"10.1016\/j.neulet.2017.03.050"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Aguzzi A, Barres BA, Bennett ML. Microglia: scapegoat, saboteur, or something else? Science. 2013;339:156-161. https:\/\/doi.org\/10.1126\/science.1227901","DOI":"10.1126\/science.1227901"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Almutairi MM, Gong C, Xu YG, Chang Y, Shi H. Factors controlling permeability of the blood-brain barrier. Cell Mol Life Sci. 2016;73:57-77. https:\/\/doi.org\/10.1007\/s00018-015-2050-8","DOI":"10.1007\/s00018-015-2050-8"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Ivanidze J, Kallas ON. Application of blood-brain barrier permeability imaging in global cerebral edema. AJNR Am J Neuroradiol. 2016;37:1599-1603. https:\/\/doi.org\/10.3174\/ajnr.A4784","DOI":"10.3174\/ajnr.a4784"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Mackman N, Bergmeier W, Stouffer GA. Therapeutic strategies for thrombosis: new targets and approaches. Nat Rev Drug Discov. 2020;19:333-352. https:\/\/doi.org\/10.1038\/s41573-020-0061-0","DOI":"10.1038\/s41573-020-0061-0"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Gilroy D, De Maeyer R. New insights into the resolution of inflammation. Semin Immunol. 2015;27:161-168. https:\/\/doi.org\/10.1016\/j.smim.2015.05.003","DOI":"10.1016\/j.smim.2015.05.003"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Patsouris V, Blecharz-Lang KG, Nieminen-Kelh\u00e4 M, Schneider UC, Vajkoczy P. Resolution of Cerebral Inflammation Following Subarachnoid Hemorrhage. Neurocrit Care. 2023;39:218-228. https:\/\/doi.org\/10.1007\/s12028-023-01770-w","DOI":"10.1007\/s12028-023-01770-w"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Geraghty JR, Davis JL, Testai FD. Neuroinflammation and microvascular dysfunction after experimental subarachnoid hemorrhage: emerging components of early brain injury related to outcome. Neurocrit Care. 2019;31:373-389. https:\/\/doi.org\/10.1007\/s12028-019-00710-x","DOI":"10.1007\/s12028-019-00710-x"},{"key":"ref44","unstructured":"Okada T, Suzuki H. Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage. Histol Histopathol. 2020;35:623-636."},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Zheng ZV, Lyu H, Lam SYE, Lam PK, Poon WS, Wong GKC. The Dynamics of Microglial Polarization Reveal the Resident Neuroinflammatory Responses After Subarachnoid Hemorrhage. Transl Stroke Res. 2020;11:433-449. https:\/\/doi.org\/10.1007\/s12975-019-00728-5","DOI":"10.1007\/s12975-019-00728-5"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Yamada H, Kase Y, Okano Y, Kim D, Goto M, Takahashi S, Okano H, Toda M. Subarachnoid hemorrhage triggers neuroinflammation of the entire cerebral cortex, leading to neuronal cell death. Inflamm Regen. 2022;42:61. https:\/\/doi.org\/10.1186\/s41232-022-00236-4","DOI":"10.1186\/s41232-022-00236-4"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Chen J, Wang L, Wu C, Hu Q, Gu C, Yan F, Li J, Yan W, Chen G. Melatonin-enhanced autophagy protects against neural apoptosis via a mitochondrial pathway in early brain injury following a subarachnoid hemorrhage. J Pineal Res. 2014;56:12-19. https:\/\/doi.org\/10.1111\/jpi.12086","DOI":"10.1111\/jpi.12086"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Chen J, Li M, Liu Z, Wang Y, Xiong K. Molecular mechanisms of neuronal death in brain injury after subarachnoid hemorrhage. Front Cell Neurosci. 2022;16:1025708. https:\/\/doi.org\/10.3389\/fncel.2022.1025708","DOI":"10.3389\/fncel.2022.1025708"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Vande Walle L, Lamkanfi M. Pyroptosis. Curr Biol. 2016;26:R568-r572. https:\/\/doi.org\/10.1016\/j.cub.2016.02.019","DOI":"10.1016\/j.cub.2016.02.019"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Liu Y, Luo Y, Zhang A, Wang Z, Wang X, Yu Q, Zhang Z, Zhu Z, Wang K, Chen L, Nie X, Zhang JH, Zhang J, Fang Y, Su Z, Chen S. Long non-coding RNA H19 promotes NLRP3-mediated pyroptosis after subarachnoid hemorrhage in rats. Transl Stroke Res. 2023;14:987-1001. https:\/\/doi.org\/10.1007\/s12975-022-01104-6","DOI":"10.1007\/s12975-022-01104-6"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Xu P, Hong Y, Xie Y, Yuan K, Li J, Sun R, Zhang X, Shi X, Li R, Wu J, Liu X, Hu W, Sun W. TREM-1 Exacerbates Neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental subarachnoid hemorrhage. Transl Stroke Res. 2021;12:643-659. https:\/\/doi.org\/10.1007\/s12975-020-00840-x","DOI":"10.1007\/s12975-020-00840-x"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Bryan NB, Dorfleutner A, Rojanasakul Y, Stehlik C. Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain. J Immunol. 2009;182:3173-3182. https:\/\/doi.org\/10.4049\/jimmunol.182.Supp.135.70, https:\/\/doi.org\/10.4049\/jimmunol.0802367","DOI":"10.4049\/jimmunol.0802367"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Sutterwala FS, Haasken S, Cassel SL. Mechanism of NLRP3 inflammasome activation. Ann N Y Acad Sci. 2014;1319:82-95. https:\/\/doi.org\/10.1111\/nyas.12458","DOI":"10.1111\/nyas.12458"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Swanson KV, Deng M. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19:477-489. https:\/\/doi.org\/10.1038\/s41577-019-0165-0","DOI":"10.1038\/s41577-019-0165-0"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. 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