Effects of atorvastatin-loaded PEGylated liposomes delivered by magnetic stimulation for stroke treatment

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation Pub Date : 2025-08-29 DOI:10.1016/j.brs.2025.08.024

Ji-Hye Kim , Ja-Hae Kim , Hafiz Ashfaq Ahmad , Hohyeon Kim , Raveena Nagareddy , Kang-Ho Choi , Jungwon Yoon , Yong-Yeon Jeong

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引用次数: 0

Abstract

Background

Focused magnetic stimulation (MagStim) can temporarily and safely open the blood-brain barrier (BBB) for target delivery. We investigated whether opening the BBB with MagStim and delivering atorvastatin-loaded PEGylated liposomes (LipoStatin) would work synergistically for subacute post-stroke treatment.

Methods

Two weeks after middle cerebral artery occlusion (MCAO), an injection of 15 mg/ml magnetic nanoparticles (MNPs) was performed, followed by 30 min of MagStim, in subacute stroke models. The procedure was conducted over a week, during which MagStim and MNPs were administered three times at two-day intervals, and LipoStatin (10 mg/kg) was injected immediately after each MagStim treatment. We investigated the motor function, BBB integrity, neuroinflammation, and neurogenesis three weeks after stroke (Sham vs. Control vs. LipoStatin vs. MagStim + LipoStatin).

Results

The MagStim + LipoStatin group showed improved motor function compared to the Control (p = 0.007) group. The MagStim + LipoStatin group significantly reduced infarct volume and improved BBB integrity compared to the control and LipoStatin groups. In the MagStim + LipoStatin group, the expression of TNF-α was reduced (p = 0.020) compared to the LipoStatin group, and eNOS was enhanced (p = 0.037) compared to the Control group. Markers for neurogenesis were also considerably increased in the MagStim + LipoStatin group compared to the Control and LipoStatin groups (p < 0.0001).

Conclusions

Our study demonstrates the beneficial synergistic effects of MagStim and the target delivery of LipoStatin in subacute ischemic stroke. These findings underscore the need for future advancements in promising novel non-invasive MagStim methods and nanotherapeutic hybrid approaches for target drug delivery and treatment in post-stroke recovery.

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磁刺激递送负载阿托伐他汀聚乙二醇脂质体对脑卒中治疗的影响

聚焦磁刺激（MagStim）可以暂时安全地打开血脑屏障（BBB）进行目标递送。我们研究了MagStim打开血脑屏障和递送装载阿托伐他汀的聚乙二醇脂质体（LipoStatin）是否会协同作用于亚急性脑卒中后治疗。方法在大脑中动脉闭塞（MCAO） 2周后，亚急性脑卒中模型注射磁性纳米颗粒（MNPs） 15 mg/ml，随后注射MagStim 30 min。该过程进行了一周，在此期间，MagStim和MNPs每两天给药三次，每次MagStim治疗后立即注射LipoStatin （10 mg/kg）。我们研究了中风后三周的运动功能、血脑屏障完整性、神经炎症和神经发生（Sham vs. Control vs. LipoStatin vs. MagStim + LipoStatin）。结果与对照组相比，MagStim + LipoStatin组运动功能明显改善（p = 0.007）。与对照组和LipoStatin组相比，MagStim + LipoStatin组显著减少梗死面积，改善血脑屏障完整性。MagStim + LipoStatin组与对照组相比，TNF-α表达降低（p = 0.020）， eNOS表达增强（p = 0.037）。与对照组和LipoStatin组相比，MagStim + LipoStatin组的神经发生标志物也显著增加（p < 0.0001）。结论在亚急性缺血性脑卒中中，MagStim与lippostatin靶向递送具有有益的协同作用。这些发现强调了未来需要在有前景的新型无创MagStim方法和纳米治疗混合方法上取得进展，以用于中风后康复的靶向药物输送和治疗。

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 Stimulation 医学-临床神经学

CiteScore

13.10

自引率

9.10%

发文量

256

审稿时长

72 days

期刊介绍： Brain Stimulation publishes on the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation. Brain Stimulation aims to be the premier journal for publication of original research in the field of neuromodulation. The journal includes: a) Original articles; b) Short Communications; c) Invited and original reviews; d) Technology and methodological perspectives (reviews of new devices, description of new methods, etc.); and e) Letters to the Editor. Special issues of the journal will be considered based on scientific merit.