Author Correction: Salvianolic acid A prevented cerebrovascular endothelial injury caused by acute ischemic stroke through inhibiting the Src signaling pathway

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt–β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague–Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood–brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of β-catenin and downstream proteins while suppressing the expression of GSK-3β. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt–β-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.

Download Full-text

Intervention Effect of Compatibility of Salvianolic Acid A & B on PDGF-C/PDGFR-α Signaling Pathway in Renal Fibrosis

Advanced Emergency Medicine ◽

10.18686/aem.v4i2.5 ◽

2015 ◽

Vol 4 (2) ◽

pp. 13

Author(s):

Bin Yu

Keyword(s):

Signaling Pathway ◽

Renal Fibrosis ◽

Kidney Tissue ◽

Renal Tissue ◽

Salvianolic Acid B ◽

Control Group ◽

Salvianolic Acid ◽

Salvianolic Acid A ◽

Drug Compatibility ◽

Renal Tubular

Objective: To explore the effect of salvianolic acid A & B component molecules of drug compatibility on PDGF-c/PDGFR-α signaling pathway in renal fibrosis of rats. Methods: 40 male SPF SD rats were randomly divided into four groups: control group, salvianolic acid A group, salvianolic acid B group and salvianolic acid A + B group, with 10 rats in each group. Each group was treated for two weeks. After the intervention, samples were collected. And scores of HE and Masson was compared. The expression of PDGF-c/PDGFR-α in rental tissue in them was also tested and compared. Results: Compared with the control group, the score of HE and Masson in intervention groups was markedly decreased, and scores in salvianolic acid B group and salvianolic acid A + B group were reduced significantly (p < 0.05); Compared with the control group, the expression of PDGF-c/PDGFR-α in rental tissue in intervention groups was lower(p < 0.05), especially in salvianolic acid B group and salvianolic acid A + B group (p < 0.05).Conclusion: salvianolic acid A & B component molecules of drug compatibility could significantly improve the pathological changes in the kidney tissue of rats, suppress the expression of PDGF-c/PDGFR-α in renal tissue, and improve the renal function, renal tubular function and renal pathology.

Download Full-text

Qingnao dripping pills mediate immune-inflammatory response and MAPK signaling pathway after acute ischemic stroke in rats

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2018.12.009 ◽

2019 ◽

Vol 139 (3) ◽

pp. 143-150 ◽

Cited By ~ 6

Author(s):

Zixiu Zeng ◽

Yunling Zhang ◽

Xiao Liang ◽

Fengli Wang ◽

Jiayi Zhao ◽

...

Keyword(s):

Ischemic Stroke ◽

Inflammatory Response ◽

Acute Ischemic Stroke ◽

Signaling Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway

Download Full-text

Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway

Brain Research ◽

10.1016/j.brainres.2016.12.007 ◽

2017 ◽

Vol 1657 ◽

pp. 279-287 ◽

Cited By ~ 15

Author(s):

De-shui Yu ◽

Yan-song Wang ◽

Yun-long Bi ◽

Zhan-peng Guo ◽

Ya-jiang Yuan ◽

...

Keyword(s):

Spinal Cord ◽

Signaling Pathway ◽

Salvianolic Acid ◽

Salvianolic Acid A ◽

Blood Spinal Cord Barrier

Download Full-text

Neurovascular protection of salvianolic acid B and ginsenoside Rg1 combination against acute ischemic stroke in rats

Neuroreport ◽

10.1097/wnr.0000000000001706 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Yao Fu ◽

Rongrong Xing ◽

Linlin Wang ◽

Li Yang ◽

Baohong Jiang

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Salvianolic Acid B ◽

Ginsenoside Rg1 ◽

Salvianolic Acid ◽

Neurovascular Protection

Download Full-text

Abstract 112: Genetic Deletion of Endothelial microRNA-15a/16-1 Promotes Cerebral Angiogenesis and Neurological Recovery in Ischemic Stroke Through Src Signaling Pathway

Stroke ◽

10.1161/str.51.suppl_1.112 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Ping Sun ◽

Feifei Ma ◽

Chao Zhou ◽

R. Anne Stetler ◽

Jun Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Brain Atrophy ◽

Conditional Knockout ◽

Neurological Recovery ◽

Targeted Deletion ◽

Post Stroke ◽

Src Signaling ◽

Genetic Deletion

Introduction: Cerebral angiogenesis is tightly controlled by certain microRNAs (miRs), such as the miR-15a/16-1 cluster, among others. Recently, we demonstrated that endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery by increasing protein levels of VEGFA, FGF2, and their receptors VEGFR2 and FGFR1. Here, we further investigated the downstream signaling pathways of these pro-angiogenic factors by using a potent Src family inhibitor, saracatinib (AZD0530), in endothelial cell-selective miR-15a/16-1 conditional knockout (EC-miR-15a/16-1 cKO) mice after ischemic stroke. Hypothesis: Pharmacological inhibition of Src signaling cascade using AZD0530 diminishes enhanced post-stroke angiogenesis and long-term neurological recovery induced by the genetic deletion of miR-15a/16-1 in the endothelium. Methods: EC-miR-15a/16-1 cKO and WT littermate controls were subjected to 1h MCAO and 28d reperfusion. AZD0530 (20 mg/kg) was administered daily to both genotypes at 3-21d after MCAO by oral gavage. Cognitive outcomes were determined by Morris water maze tests. Brain atrophy was measured by MAP2 immunostaining. Cerebral blood flow (CBF) was monitored by laser speckle imaging. Brain capillary density and functional vessels were examined by CD31/BrdU and tomato lectin/BrdU double-immunostaining, respectively. Src signaling pathway-related molecules were analyzed by western blotting. Results: Treatment with AZD0530 exacerbates cognitive impairments and brain atrophy in EC-miR-15a/16-1 cKO mice following MCAO. AZD0530 also attenuates the long-term CBF recovery, correlated with inhibiting the generation of newly formed microvessels and functional vessels in the peri-infarct brain regions in EC-miR-15a/16-1 cKO mice after cerebral ischemia. Moreover, EC-targeted deletion of miR-15a/16-1 upregulates the Src signaling pathway, while AZD0530 blocks the Src signaling pathway by downregulating p-Src and its downstream mediators (p-Stat3, p-Akt, p-FAK, p-p38 MAPK) in ischemic brains. Conclusions: Endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery via Src signaling pathway.

Download Full-text

A DNA Nanostructure-Based Neuroprotectant against Neuronal Apoptosis via Inhibiting Toll-like Receptor 2 Signaling Pathway in Acute Ischemic Stroke

ACS Nano ◽

10.1021/acsnano.1c09626 ◽

2021 ◽

Author(s):

Mi Zhou ◽

Tianxu Zhang ◽

Bowen Zhang ◽

Xiaolin Zhang ◽

Shaojingya Gao ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Signaling Pathway ◽

Neuronal Apoptosis ◽

Toll Like Receptor ◽

Dna Nanostructure ◽

Toll Like Receptor 2

Download Full-text

Cerebral Protection of Salvianolic Acid A by the Inhibition of Granulocyte Adherence

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11008683 ◽

2011 ◽

Vol 39 (01) ◽

pp. 111-120 ◽

Cited By ~ 20

Author(s):

Min Jiang ◽

Xiao-Ying Wang ◽

Wang-Yi Zhou ◽

Jing Li ◽

Jie Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

Vascular Endothelial Cells ◽

Leukocyte Adhesion ◽

Ischemia Reperfusion ◽

Experimental Studies ◽

Cerebral Protection ◽

Active Components ◽

Salvianolic Acid ◽

Salvianolic Acid A ◽

Adhesion Rate

Ischemic stroke is one of the most common causes of death and disability that is induced by ischemia reperfusion (IR). Granulocyte adherence has been proven to be a principal cause of IR. Salvianolic acid A (Sal A) is one of the major active components of Danshen, a Chinese herbal medicine used for the treatment of cardiovascular and cerebrovascular diseases, such as ischemic stroke. Some experimental studies have shown the strong cerebral protection effect of Sal A. However, little information is available about the effect of Sal A on granulocyte adherence to brain micro-vascular endothelial cells (BMEC). Therefore, the aim of the present study was to investigate the effect of Sal A on the leukocyte adhesion rate and the intercellular cell adhesion molecule-1 (ICAM-1) expression in BMEC injured by hypoxia/reoxygenation (H/R), using a rheometer, qRT-PCR, and flow cytometry (FCM). The results of the adhesion rate gathered by the rheometer showed that Sal A could remarkably inhibit the adherence of granulocytes on BMEC in the case of H/R injury. Moreover, PCR and FCM results showed that Sal A could decrease the expression of ICAM-1 on BMEC on the gene and protein levels. In conclusion, the study demonstrated that the inhibition of granulocyte adherence is one of the targets of Sal A in the treatment of ischemic stroke. Meanwhile, Sal A inhibits of granulocyte adherence by decreasing the expression of ICAM-1 in BMEC.

Download Full-text