Aquaporin-4 activation facilitates glymphatic system function and hematoma clearance post-intracerebral hemorrhage.

IF 5.4 2区 医学 Q1 NEUROSCIENCES
Glia Pub Date : 2025-02-01 Epub Date: 2024-11-12 DOI:10.1002/glia.24639
Wenchao Chen, Chuntian Liang, Shasha Peng, Shuangjin Bao, Fang Xue, Xia Lian, Yinghong Liu, Gaiqing Wang
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引用次数: 0

Abstract

Efficient clearance of hematomas is crucial for improving clinical outcomes in patients with intracerebral hemorrhage (ICH). The glymphatic system, facilitated by aquaporin-4 (AQP4), plays a crucial role in cerebrospinal fluid (CSF) entry and metabolic waste clearance. This study examined the role of the glymphatic system in ICH pathology, with a focus on AQP4. Collagenase-induced ICH models were established, with AQP4 expression regulated through mifepristone as an agonist, TGN-020 as an inhibitor, and Aqp4 gene knockout. Fluorescence tracing and multimodal magnetic resonance imaging (MRI) were employed to observe glymphatic system functionality, hematoma, and edema volumes. Neurological deficit scoring was performed using the modified Garcia Scale. AQP4 expression was quantified using RT-qPCR and Western blotting, and cellular localization was explored using immunofluorescence. The brain tissue sections were examined for neuronal morphology, degenerative changes, and iron deposition. Three days post-ICH, the AQP4 agonist group showed increased AQP4 protein expression and perivascular polarization, decreased hemoglobin levels, and reduced iron deposition. Conversely, the inhibition group exhibited contrasting trends. AQP4 activation improved glymphatic system function, leading to a wider distribution, improved neurological function, and reduced hematoma. Pharmacological inhibition and genetic knockout of AQP4 have opposing effects. The glymphatic system, facilitated by AQP4, plays a crucial role in hematoma clearance following cerebral hemorrhage. Upregulation of AQP4 improves glymphatic system function, facilitates hematoma clearance, and promotes brain tissue recovery.

激活Aquaporin-4有助于脑出血后的肾上腺系统功能和血肿清除。
有效清除血肿对改善脑内出血(ICH)患者的临床疗效至关重要。由水汽蛋白-4(AQP4)促进的甘油系统在脑脊液(CSF)进入和代谢废物清除中发挥着至关重要的作用。本研究以 AQP4 为重点,探讨了甘液系统在 ICH 病理学中的作用。研究人员建立了胶原酶诱导的 ICH 模型,通过米非司酮作为激动剂、TGN-020 作为抑制剂以及 Aqp4 基因敲除来调节 AQP4 的表达。采用荧光追踪和多模态磁共振成像(MRI)观察甘回流系统功能、血肿和水肿体积。采用改良加西亚量表对神经功能缺损进行评分。使用 RT-qPCR 和 Western 印迹法量化 AQP4 的表达,并使用免疫荧光法检测细胞定位。对脑组织切片进行神经元形态、退行性变化和铁沉积检查。脑梗死三天后,AQP4 激动剂组显示 AQP4 蛋白表达和血管周围极化增加,血红蛋白水平降低,铁沉积减少。相反,抑制组则呈现出截然不同的趋势。激活 AQP4 可改善甘液系统功能,使其分布更广,改善神经功能,减少血肿。药物抑制和基因敲除 AQP4 的效果截然相反。在 AQP4 的促进下,甘液系统在脑出血后的血肿清除中发挥着至关重要的作用。上调 AQP4 可改善甘液系统功能,促进血肿清除,促进脑组织恢复。
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
Glia
Glia 医学-神经科学
CiteScore
13.10
自引率
4.80%
发文量
162
审稿时长
3-8 weeks
期刊介绍: GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.
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