The upregulation of caveolin-1 expression via the TLR4-Myd88 pathway contributes to cerebral vasospasm.

IF 1.5 4区 医学 Q3 CLINICAL NEUROLOGY
Neurological Research Pub Date : 2025-07-01 Epub Date: 2025-04-22 DOI:10.1080/01616412.2025.2491778
Quan Yan, Tai'an Fang, Xuefei Liu, Guojia Du
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引用次数: 0

Abstract

Cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH) significantly impacts patient morbidity and mortality. This study aimed to investigate the role of the TLR4-MyD88 signaling pathway in the pathogenesis of CVS and its relationship with Caveolin-1 (CAV-1). We established a rat model of SAH using the double blood injection method in the cisterna magna to induce CVS. Various techniques, including pathological assessments, immunohistochemistry, Western blotting, and RT-qPCR, were employed to evaluate the expression of Toll-like receptor 4 (TLR4), MyD88, NF-κB, and CAV-1. The results showed a significant upregulation of TLR4, MyD88, NF-κB, and CAV-1 in SAH rats, with the upregulation correlating with CVS. Furthermore, the application of methyl-β-cyclodextrin (MβCD) effectively reduced CAV-1 expression and ameliorated CVS severity. Additionally, dexmedetomidine (DEX) treatment downregulated inflammatory markers and improved CVS, suggesting a potential therapeutic role through modulating the TLR4-MyD88 pathway. This study highlights the complex interplay between neuroinflammation, CAV-1, and CVS, proposing new avenues for therapeutic interventions in managing CVS post-SAH.

通过TLR4-Myd88途径上调caveolin-1的表达有助于脑血管痉挛。
蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)显著影响患者的发病率和死亡率。本研究旨在探讨TLR4-MyD88信号通路在CVS发病中的作用及其与Caveolin-1 (CAV-1)的关系。我们采用大池双血注射法诱导CVS,建立大鼠SAH模型。采用病理评估、免疫组织化学、Western blotting和RT-qPCR等多种技术评估toll样受体4 (TLR4)、MyD88、NF-κB和CAV-1的表达。结果显示,SAH大鼠TLR4、MyD88、NF-κB、CAV-1表达显著上调,且上调与CVS相关。此外,甲基β-环糊精(m -β cd)的应用可以有效降低CAV-1的表达,改善CVS的严重程度。此外,右美托咪定(DEX)治疗下调炎症标志物并改善CVS,表明通过调节TLR4-MyD88途径具有潜在的治疗作用。这项研究强调了神经炎症、CAV-1和CVS之间复杂的相互作用,为sah后CVS的治疗干预提出了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neurological Research
Neurological Research 医学-临床神经学
CiteScore
3.60
自引率
0.00%
发文量
116
审稿时长
5.3 months
期刊介绍: Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.
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