Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage

IF 3.5 3区医学 Q2 NEUROSCIENCES Brain Research Bulletin Pub Date : 2024-08-05 DOI:10.1016/j.brainresbull.2024.111045

Junbo Liao , Yingxing Duan , Yaxue Liu , Haolong Chen , Zhihan An , Yibing Chen , Zhangjie Su , Ahsan Muhammad Usman , Gelei Xiao

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Abstract

Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution in the acute phase of ICH, though the precise mechanisms remain unclear. Recent findings have highlighted the glymphatic system (GS) as a crucial component in intracranial cerebrospinal fluid circulation, playing a significant role in hematoma clearance post-ICH. This study investigates the link between SIM efficacy in hematoma resolution and the GS. Our experimental results show that SIM alleviates GS damage in ICH-induced rats, resulting in improved outcomes such as reduced brain edema, neuronal apoptosis, and degeneration. Further analysis reveals that SIM's effects are mediated through the VEGF-C/VEGFR3/PI3K-Akt pathway. This study advances our understanding of SIM's mechanism in promoting intracranial hematoma clearance and underscores the potential of targeting the GS for ICH treatment.

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辛伐他汀通过血管内皮生长因子-C/血管内皮生长因子受体3/PI3K-Akt途径减轻实验性脑出血后的甘油系统损伤。

由于缺乏有效的药物疗法，目前的临床实践主要依靠外科手术清除脑内出血（ICH）患者的血肿。以往的研究表明，辛伐他汀（SIM）可促进 ICH 急性期血肿的吸收和消散，但其确切机制仍不清楚。最近的研究结果表明，甘油系统（GS）是颅内脑脊液循环的重要组成部分，在 ICH 后血肿清除中发挥着重要作用。本研究探讨了 SIM 在血肿清除方面的疗效与 GS 之间的联系。我们的实验结果表明，SIM 可减轻 ICH 大鼠的 GS 损伤，从而改善脑水肿、神经元凋亡和变性等结果。进一步分析表明，SIM 的作用是通过 VEGF-C/VEGFR3/PI3K-Akt 通路介导的。这项研究加深了我们对 SIM 促进颅内血肿清除机制的理解，并强调了以 GS 为靶点治疗 ICH 的潜力。

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

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.