Shuyuan Hu, Yaqin Gu, Limin Hou, Jia Liu, Haiping Zhao, Yumin Luo, Chunxiu Wang, Xunming Ji, Guiyou Liu, Jiangang Duan
{"title":"类固醇在严重脑静脉血栓中的神经保护潜力：抑制 NLRP3 炎症球体的实验和临床探索。","authors":"Shuyuan Hu, Yaqin Gu, Limin Hou, Jia Liu, Haiping Zhao, Yumin Luo, Chunxiu Wang, Xunming Ji, Guiyou Liu, Jiangang Duan","doi":"10.1111/cns.70125","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>NLRP3 inflammasome-related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti-inflammatory agents in improving severe CVT prognosis remains controversial.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A total of 94 male Sprague–Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In rats, compared with the sham group, NLRP3-related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, <i>p</i> < 0.01; pro-Caspase-1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, <i>p</i> < 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, <i>p</i> < 0.05; pro-IL-1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, <i>p</i> < 0.01), decreased on day 7 in rats (<i>n</i> = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, <i>p</i> < 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, <i>p</i> < 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL-6 levels correlated positively with NIHSS (<i>r</i> = 0.4273, <i>p</i> = 0.0020; <i>r</i> = 0.4938, <i>p</i> = 0.0029) and mRS (<i>r</i> = 0.5349, <i>p</i> = 0.0125; <i>r</i> = 0.6213, <i>p</i> = 0.026), while CSF IL-6 correlated positively with mRS on admission (<i>r</i> = 0.5349, <i>p</i> = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), <i>p</i> < 0.0001) and IL-6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, <i>p</i> < 0.05), accompanying by improvement of neurological deficits and CSF circulation (all <i>p</i> < 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow-up. No significant steroid-related adverse effects were observed.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Short-term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome-related inflammation.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70125","citationCount":"0","resultStr":"{\"title\":\"Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition\",\"authors\":\"Shuyuan Hu, Yaqin Gu, Limin Hou, Jia Liu, Haiping Zhao, Yumin Luo, Chunxiu Wang, Xunming Ji, Guiyou Liu, Jiangang Duan\",\"doi\":\"10.1111/cns.70125\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>NLRP3 inflammasome-related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti-inflammatory agents in improving severe CVT prognosis remains controversial.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>A total of 94 male Sprague–Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In rats, compared with the sham group, NLRP3-related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, <i>p</i> < 0.01; pro-Caspase-1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, <i>p</i> < 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, <i>p</i> < 0.05; pro-IL-1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, <i>p</i> < 0.01), decreased on day 7 in rats (<i>n</i> = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, <i>p</i> < 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, <i>p</i> < 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL-6 levels correlated positively with NIHSS (<i>r</i> = 0.4273, <i>p</i> = 0.0020; <i>r</i> = 0.4938, <i>p</i> = 0.0029) and mRS (<i>r</i> = 0.5349, <i>p</i> = 0.0125; <i>r</i> = 0.6213, <i>p</i> = 0.026), while CSF IL-6 correlated positively with mRS on admission (<i>r</i> = 0.5349, <i>p</i> = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), <i>p</i> < 0.0001) and IL-6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, <i>p</i> < 0.05), accompanying by improvement of neurological deficits and CSF circulation (all <i>p</i> < 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow-up. No significant steroid-related adverse effects were observed.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Short-term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome-related inflammation.</p>\\n </section>\\n </div>\",\"PeriodicalId\":154,\"journal\":{\"name\":\"CNS Neuroscience & Therapeutics\",\"volume\":\"30 11\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-11-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70125\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS Neuroscience & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cns.70125\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70125","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition
Background
NLRP3 inflammasome-related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti-inflammatory agents in improving severe CVT prognosis remains controversial.
Methods
A total of 94 male Sprague–Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients.
Results
In rats, compared with the sham group, NLRP3-related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, p < 0.01; pro-Caspase-1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, p < 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, p < 0.05; pro-IL-1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, p < 0.01), decreased on day 7 in rats (n = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, p < 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, p < 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL-6 levels correlated positively with NIHSS (r = 0.4273, p = 0.0020; r = 0.4938, p = 0.0029) and mRS (r = 0.5349, p = 0.0125; r = 0.6213, p = 0.026), while CSF IL-6 correlated positively with mRS on admission (r = 0.5349, p = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), p < 0.0001) and IL-6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, p < 0.05), accompanying by improvement of neurological deficits and CSF circulation (all p < 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow-up. No significant steroid-related adverse effects were observed.
Conclusion
Short-term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome-related inflammation.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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