Sult2b1 Modulates NLRP3/BCL-2 Signaling and Pro-Inflammatory Microglial/Macrophage Polarization After Traumatic Brain Injury.

IF 3.2 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2026-09-18 DOI:10.2174/0109298673532074260901055730

Hao Zhang, Zhenhong Pan, Hua Chen, Yinxing Huang, Shousen Wang

{"title":"Sult2b1 Modulates NLRP3/BCL-2 Signaling and Pro-Inflammatory Microglial/Macrophage Polarization After Traumatic Brain Injury.","authors":"Hao Zhang, Zhenhong Pan, Hua Chen, Yinxing Huang, Shousen Wang","doi":"10.2174/0109298673532074260901055730","DOIUrl":null,"url":null,"abstract":"Introduction: Traumatic Brain Injury (TBI) causes prolonged neurological impairment through primary mechanical damage and secondary cascades including neuroinflammation and apoptosis. This study investigated whether Sult2b1, a cholesterol sulfation enzyme, protects against secondary injury after TBI.Methods: A Controlled Cortical Impact (CCI) mouse model was used. Sult2b1 expression was assessed by RT-qPCR and western blotting. AAV-mediated delivery restored Sult2b1, and its effects were evaluated via histology, immunofluorescence, imaging, ELISA, and behavioral tests.Results: Sult2b1 was markedly downregulated after TBI. Overexpression improved cerebral blood flow, preserved neurons, reduced apoptosis, decreased TNF-α and IL-1β, and increased IL-4. Mechanistically, it modulated NLRP3/BCL-2 and suppressed M1-like microglial/macrophage polarization. Functionally, it enhanced sensorimotor and cognitive performance and reduced lesion volume and chronic tissue loss.Discussion: Our findings identify Sult2b1 as an endogenous protective factor that limits neuroinflammation and promotes neuronal survival via NLRP3/BCL-2 and microglial polarization modulation, suggesting therapeutic potential.Conclusion: Sult2b1 confers neuroprotection after TBI and may serve as a potential target for reducing secondary brain injury.","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0109298673532074260901055730","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Traumatic Brain Injury (TBI) causes prolonged neurological impairment through primary mechanical damage and secondary cascades including neuroinflammation and apoptosis. This study investigated whether Sult2b1, a cholesterol sulfation enzyme, protects against secondary injury after TBI.

Methods: A Controlled Cortical Impact (CCI) mouse model was used. Sult2b1 expression was assessed by RT-qPCR and western blotting. AAV-mediated delivery restored Sult2b1, and its effects were evaluated via histology, immunofluorescence, imaging, ELISA, and behavioral tests.

Results: Sult2b1 was markedly downregulated after TBI. Overexpression improved cerebral blood flow, preserved neurons, reduced apoptosis, decreased TNF-α and IL-1β, and increased IL-4. Mechanistically, it modulated NLRP3/BCL-2 and suppressed M1-like microglial/macrophage polarization. Functionally, it enhanced sensorimotor and cognitive performance and reduced lesion volume and chronic tissue loss.

Discussion: Our findings identify Sult2b1 as an endogenous protective factor that limits neuroinflammation and promotes neuronal survival via NLRP3/BCL-2 and microglial polarization modulation, suggesting therapeutic potential.

Conclusion: Sult2b1 confers neuroprotection after TBI and may serve as a potential target for reducing secondary brain injury.

查看原文本刊更多论文

Sult2b1调节创伤性脑损伤后NLRP3/BCL-2信号和促炎小胶质细胞/巨噬细胞极化

外伤性脑损伤（TBI）通过原发性机械损伤和继发性级联反应（包括神经炎症和细胞凋亡）引起长期的神经功能损害。本研究探讨了胆固醇硫酸化酶Sult2b1是否对脑外伤后的继发性损伤有保护作用。方法：采用控制性皮质冲击（CCI）小鼠模型。RT-qPCR和western blotting检测Sult2b1的表达。aav介导的递送可恢复Sult2b1，并通过组织学、免疫荧光、成像、ELISA和行为测试评估其效果。结果：脑外伤后Sult2b1明显下调。过表达可改善脑血流量，保存神经元，减少细胞凋亡，降低TNF-α和IL-1β，升高IL-4。机制上，它调节NLRP3/BCL-2，抑制m1样小胶质细胞/巨噬细胞极化。在功能上，它增强了感觉运动和认知能力，减少了病变体积和慢性组织损失。讨论：我们的研究结果确定Sult2b1是一种内源性保护因子，通过NLRP3/BCL-2和小胶质极化调节来限制神经炎症并促进神经元存活，提示治疗潜力。结论：Sult2b1在脑外伤后具有神经保护作用，可能是减少继发性脑损伤的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.