Proteoglycan 4 attenuates ischemic post-stroke hemorrhagic transformation and blood-brain barrier disruption

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-09-21 DOI:10.1016/j.ibneur.2025.09.008

Jing Yang , Ning Tang , Ruanxian Dai , Jiajie Chen , Zhaojiao Li , Fengwen Jiang , Shiyi Li , Qiang Meng

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Abstract

Background

Proteoglycan 4 (PRG4) possesses biological characteristics of anti-inflammation, lubrication, anti-apoptosis, and immunomodulation, and regulates the homeostasis of articular cartilage, myocardium, brain, and skin tissues. Nevertheless, the function of PRG4 in post-stroke hemorrhagic transformation (HT) and blood-brain barrier (BBB) disruption is unknown.

Methods

A post-stroke HT mouse model (MACO-HT) was constructed and subsequently treated with recombinant PRG4 by tail vein injection. Neurologic impairment in mice was evaluated using mNSS and Zea longa score. The effect of recombinant PRG4 on HT was assessed using HE and TTC staining and hemoglobin assays. The effect of recombinant PRG4 on BBB repair was evaluated using Evan's blue leakage, western blotting, and IF staining assays.

Results

Recombinant PRG4 reduced mNSS and Zea longa scores in MACO-HT mice. Infarct and hemorrhage areas and hemoglobin level in brain tissues of MACO-HT mice were significantly diminished after treatment with recombinant PRG4. MACO-HT mice exhibited significant Evan's blue leakage, which was ameliorated by reconstituted PRG4. Moreover, recombinant PRG4 notably diminished the levels of TLR2, MMP-2, and MMP-9 proteins, and augmented the levels of Claudin-5, Occludin, and ZO-1 in the brain tissues of MACO-HT mice.

Conclusion

Recombinant PRG4 ameliorated post-stroke neurological impairment, HT, and BBB disruption. This finding identifies a biological function for PRG4 in stroke and provides support for therapeutic strategies targeting HT and BBB injury.

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蛋白多糖4减轻缺血性脑卒中后出血转化和血脑屏障破坏

蛋白多糖4 （PRG4）具有抗炎、润滑、抗细胞凋亡和免疫调节的生物学特性，并调节关节软骨、心肌、脑和皮肤组织的稳态。然而，PRG4在脑卒中后出血转化（HT）和血脑屏障（BBB）破坏中的功能尚不清楚。方法建立脑卒中后HT小鼠模型（MACO-HT），经尾静脉注射重组PRG4。采用mNSS和Zea longa评分评价小鼠神经功能损害。通过HE、TTC染色和血红蛋白检测评估重组PRG4对HT的影响。重组PRG4对血脑屏障修复的影响采用Evan蓝漏、western blotting和IF染色法进行评估。结果重组PRG4降低了MACO-HT小鼠的mNSS和Zea longa评分。重组PRG4处理后，MACO-HT小鼠脑组织梗死出血面积和血红蛋白水平均显著降低。MACO-HT小鼠出现明显的Evan’s蓝漏，重组PRG4可改善Evan’s蓝漏。此外，重组PRG4显著降低了MACO-HT小鼠脑组织中TLR2、MMP-2和MMP-9蛋白的水平，并增加了Claudin-5、Occludin和ZO-1蛋白的水平。结论重组PRG4可改善脑卒中后神经功能障碍、HT和血脑屏障破坏。这一发现确定了PRG4在卒中中的生物学功能，并为针对HT和血脑屏障损伤的治疗策略提供了支持。

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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