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

Hyperuricemia is closely related to acute ischemic stroke (AIS). In our study, we investigated the pattern of miRNA-155-5p and miRNA-124-5p expressions along with its clinical application in AIS and hyperuricemia patients and in a hyperuricemia rat model by RT-qPCR. The hyperuricemia rat model was established, and we found that the levels of miRNA-155-5p and miRNA-124-5p were increased in the serum, brain and kidney tissues compared with those in the normal rats. We proved that the levels of miRNA-155-5p and miRNA-124-5p were also elevated in AIS, hyperuricemia and AIS accompanied with hyperuricemia patients enrolled from the department of neurology in Inner Mongolia People’s Hospital (IMPH). The miRNA-155-5p and miRNA-124-5p were mainly associated with neuronal apoptosis, cerebral vasospasm, neuron projection, neuron projection morphogenesis, neuron differentiation and exocytosis. The above results might provide clues for the study the pathogenesis of AIS and hyperuricemia.

Download Full-text

Restoration of L-OPA1 alleviates acute ischemic stroke injury in rats via inhibiting neuronal apoptosis and preserving mitochondrial function

Redox Biology ◽

10.1016/j.redox.2020.101503 ◽

2020 ◽

Vol 34 ◽

pp. 101503 ◽

Cited By ~ 5

Author(s):

Yongxing Lai ◽

Peiqiang Lin ◽

Manli Chen ◽

Yixian Zhang ◽

Jianhao Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Mitochondrial Function ◽

Neuronal Apoptosis

Download Full-text

Toll like receptor 2 signaling pathway in endothelial barrier regulation

The FASEB Journal ◽

10.1096/fasebj.25.1_supplement.114.2 ◽

2011 ◽

Vol 25 (S1) ◽

Author(s):

Agnieszka Jezierska‐Drutel ◽

Irina Kolosova ◽

Alexander D Verin

Keyword(s):

Signaling Pathway ◽

Endothelial Barrier ◽

Toll Like Receptor ◽

Toll Like Receptor 2 ◽

Barrier Regulation

Download Full-text

Inhibition of Toll-Like Receptor-4 (TLR-4) Improves Neurobehavioral Outcomes After Acute Ischemic Stroke in Diabetic Rats: Possible Role of Vascular Endothelial TLR-4

Molecular Neurobiology ◽

10.1007/s12035-018-1184-8 ◽

2018 ◽

Vol 56 (3) ◽

pp. 1607-1617 ◽

Cited By ~ 7

Author(s):

Yasir Abdul ◽

Mohammed Abdelsaid ◽

Weiguo Li ◽

R. Clinton Webb ◽

Jennifer C. Sullivan ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Diabetic Rats ◽

Vascular Endothelial ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Neurobehavioral Outcomes

Download Full-text

Abstract 2874: Functional Polymorphisms in Toll-like Receptor 4 Predict Worse Outcome in Acute Ischemic Stroke Patients

Stroke ◽

10.1161/str.43.suppl_1.a2874 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Jonathan R Weinstein ◽

Juliane Schulze ◽

Richard V Lee ◽

Dannielle Zierath ◽

Patricia Tanzi ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Immune Cell ◽

Stroke Severity ◽

Multiple Time ◽

Toll Like Receptor ◽

C Reactive Protein ◽

Toll Like Receptor 4 ◽

Reactive Protein ◽

Functional Polymorphisms

Background: Toll-like receptor-4 (TLR4) plays a central role in the pathophysiology of acute ischemic stroke (AIS). Specific single nucleotide polymorphisms (SNPs) in TLR4 including 1063 A/G [Asp299Gly] and 1363 C/T [Thr399Ile] alter immune cell responsiveness to lipopolysaccharide (LPS) and are associated with increased rates of infection. The effect of these TLR4 SNPs on outcome following AIS is unknown. Methods: Patients were prospectively enrolled after onset of AIS. Clinical and demographic data were collected and neurological outcomes assessed at 3 months. Blood was drawn at multiple time points to quantify leukocyte subsets and assess plasma levels of C-reactive protein and a panel of cytokines. Genotyping for the TLR4 SNPs was also performed on blood samples. Uni- and multivariate analyses were performed to assess associations between TLR4 SNP haplotype and (i) each laboratory parameter noted above, (ii) infection risk and (iii) stroke outcome. Results: Of the 42 patients included; 6 (14%) were heterozygous for either one or both TLR4 SNPs. Baseline characteristics were similar in patients with or without a TLR4 SNP. In analyses adjusted for both initial stroke severity and age, the presence of a TLR4 SNP was associated with increases in blood leukocytes, plasma C-reactive protein and the cytokine interleukin-1 receptor antagonist (IL-1ra). The presence of either TLR4 SNP was also associated with a trend toward increased rates of infection (adjusted odds ratio and 95% confidence interval of 8.20 and 0.826-81.5, respectively) and a decreased likelihood of favorable outcome as defined by a modified Rankin Scale score of two or less at three months from stroke onset (0.014, 0.00-0.759). Conclusions: In AIS patients, functionally significant genetic variations in TLR4 influence both rates of stroke-associated infection and neurological outcome. These data suggest a direct connection between TLR4 function and stroke pathophysiology.

Download Full-text

microRNA-195 attenuates neuronal apoptosis in rats with ischemic stroke through inhibiting KLF5-mediated activation of the JNK signaling pathway

Molecular Medicine ◽

10.1186/s10020-020-00150-w ◽

2020 ◽

Vol 26 (1) ◽

Cited By ~ 4

Author(s):

Lisha Chang ◽

Wan Zhang ◽

Songxin Shi ◽

Yanbo Peng ◽

Dali Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Neuronal Apoptosis ◽

Jnk Signaling ◽

Jnk Signaling Pathway

Download Full-text

IM-12 activates the Wnt–β-catenin signaling pathway and attenuates rtPA-induced hemorrhagic transformation in rats after acute ischemic stroke

Biochemistry and Cell Biology ◽

10.1139/bcb-2018-0384 ◽

2019 ◽

Vol 97 (6) ◽

pp. 702-708 ◽

Cited By ~ 3

Author(s):

Ting Wang ◽

Yu-Mei Duan ◽

Qiao Fu ◽

Tao Liu ◽

Jin-Cheng Yu ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Signaling Pathway ◽

Glycogen Synthase ◽

Hemorrhagic Transformation ◽

Neurological Deficits ◽

Control Group ◽

High Morbidity ◽

Sprague Dawley ◽

Gsk 3Β

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