Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition

IF 4.8 1区医学 Q1 NEUROSCIENCES CNS Neuroscience & Therapeutics Pub Date : 2024-11-17 DOI:10.1111/cns.70125

Shuyuan Hu, Yaqin Gu, Limin Hou, Jia Liu, Haiping Zhao, Yumin Luo, Chunxiu Wang, Xunming Ji, Guiyou Liu, Jiangang Duan

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Abstract

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.

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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。

背景：NLRP3炎症体相关炎症可能在重症CVT的病理生理学中扮演重要角色。使用类固醇作为抗炎药物改善重度 CVT 预后仍存在争议：方法：共使用了 94 只雄性 Sprague-Dawley 大鼠。我们评估了严重 CVT 大鼠和/或患者大脑、血液和脑脊液中 NLRP3 炎性体的动态变化及其与严重程度之间的关联。我们还探讨了类固醇对动物和/或患者 CVT 后 NLRP3 活化、神经损伤和 CSF 循环障碍的影响：结果：与假组相比，大鼠的 NLRP3 相关因子在第 1 天升高，在第 2 天达到峰值（NLRP3，假组：0.79 ± 0.22；第 2 天：1.25 ± 0.08，p 结论：短期类固醇治疗可改善大鼠和/或患者的前体损伤：短期类固醇治疗可抑制 NLRP3 炎症相关炎症，从而改善重症 CVT 的预后。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

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.