Lingxiao Zhang1,2  · Yanan Shao2,3  · Zhao Fang2,3  · Siqi Chen4  · Yixuan Wang2,3  · Han Sha4  · Yuhan Zhang4  · Linlin Wang2  · Yi Jin5  · Hao Chen2,3  · Baohong Jiang1,2,3,4

1 School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China 

2 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China 

3 University of Chinese Academy of Sciences, Beijing 100049, China 

4 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China 

5 Shenzhen Institute for Drug Control (Shenzhen Testing Center of Medical Devices), Shenzhen 518057, China

Abstract

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.

Keywords

Cerebral edema; Glymphatic system; Ischemic stroke; SalB/Rg1; MMP9; AQP4

[SpringerLink]