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(...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 cleavedβ-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.展开更多
基金supported by Zhao Guoping Academician Workstation(Hangzhou Academician Workstation)of Zhejiang Chinese Medical University,Chinese Academy of Sciences-the Alliance of National and International Science Organizations for the Belt and Road Regions Fellowship(CAS-ANSO-FP-2024-06)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1060000)the Science and Technology Commission of Shanghai Municipality(No.YDZX20233100004032001,China).
文摘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 cleavedβ-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.