Abstract 2628: Remote Ischemic Conditioning Reduces Brain Edema in Experimental Ischemia/Reperfusion Injury

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Changhong Ren ◽  
Mingqing Gao ◽  
Ning Li ◽  
Jinqiang Cao ◽  
Yuchuan Ding ◽  
...  
Keyword(s):  
Tight Junction ◽  
Brain Edema ◽  
Treated Group ◽  
Tight Junction Protein ◽  
Control Group ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Mca Occlusion ◽  
Junction Protein ◽  
And Control

Background and Purpose _Remote ischemic conditioning (RIC) has been shown to provide neuroprotective effects, but the precise mechanisms underlying the therapeutic effects still remain unclear. In this study, we investigate changes in blood-brain barrier (BBB) permeability and edema formation, in association with expression of matrix metalloproteinases (MMP), tight junction proteins and aquaporins (AQP) in RIC treated rats following unilateral middle cerebral artery (MCA) occlusion and reperfusion. Methods _Ischemic stroke model was generated by occlusion of the right MCA for 1.5 hours in male Sprague-Dawley rats. Remote ischemic conditioning was conducted immediately after MCA occlusion in the bilateral lower limb by occluding and releasing the femoral artery for three cycles; each occlusion and release lasted for 10 minutes. Edema levels and BBB integrity were studied by quantification of brain water content and extravasations of Evans blue at 48 hours after reperfusion, respectively. Protein expression of occludin, claudin-5, ZO-1, MMP-2, MMP-9, as well as AQP-4 and AQP-9, were determined by Western blot analysis at 48 hours after reperfusion. The activity of MMP-2 and MMP-9 were determined by gelatin zymography at the same time points. Results _Treatment with RIC significantly ( P <0.05) reduced brain edema ( P <0.01) and BBB dysfunction when compared to the control ischemic groups. IPC treatment resulted in a significant ( P <0.05) increase in the expression of tight junction protein occludin in comparison to the control non-treatment group. The expressions of claudin-5 and ZO-1were not different between RIC-treated group and control group. RIC treatment diminished ischemia-induced MMP-9 ( P <0.01) but not MMP-2. The expressions of AQP-4 and AQP-9 were not different between RIC-treated group and control group. Conclusions _RIC ameliorates brain edema and BBB disruption after stroke, in association with a reduction of MMP-9 and increase in the expression of tight junction protein occludin. These results provide clues to neuroprotective properties of RIC.

Abstract 17162: Ambient Ultra Fine Particle Exposure Impairs Gut Vascular Barrier via Notch Signaling

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Chih-Chiang Chang ◽  
Kyung In Baek ◽  
Yichen Ding ◽  
Constantinos Sioutas ◽  
Rongsong Li ◽  
...  
Keyword(s):  
Tight Junction ◽  
Notch Signaling ◽  
Ambient Air ◽  
Air Pollutant ◽  
Gastrointestinal System ◽  
Tight Junction Protein ◽  
Control Group ◽  
Phenol Red ◽  
Dependent Manner ◽  
Junction Protein

Introduction: Ultrafine particles (UFP, d < 0.1 μm), a major sub-fraction of particulate matter (PM 2.5 , d < 2.5μm) in air pollutant, have been reported to increase cardiovascular morbidity. UFP promote endothelial dysfunction/permeability associated with Notch inhibition and degradation of tight junction protein. Gut vascular barrier (GVB) is a distinct protective barrier that inhibits translocations of antigens across the gut lumen, preventing infections by oral digestions. Here, we hypothesized UFP impair GVB by attenuating Notch signaling and disrupting tight junction protein. Method: The transgenic Tg( flk1:mCherry ) zebrafish embryos were immobilized in neutralized tricaine solution and mounted in 2% low melting agarose to perform micro-gavage at 5 days post fertilizations (5dpf). A mA mixture of 10 kD FITC conjugated dextran and phenol red dye wasere micro-gavaged on the intestinal bulb with or without UFP at 25 μg/mL. Anterior trunk and posterior cardinal vein (PCV) post micro-gavage were imaged under a confocal microscope. Notch signaling related genes including the Notch ligand, Dll4, and the target, HES1, and the level of tight junction protein genes zonula occludens-1 (ZO-1) and Occludin (OCLN) mRNA expression following different courses of exposure to UFP were assessed in Human Aortic Endothelial Cells (HAEC) with quantitative RT-PCR., Result: In the control group, the majority of FITC-dextran remained inside the gastrointestinal system. On the other hand, UFP exposure developed a significant accumulation of FITC-dextran in the intersomatic spaces (ISS) between the dorsal aorta (DA) and the PCV. This finding supports evidence of UFP exposure disrupted both the epithelial boundary and the endothelial vascular layer of the gut. In addition, Notch signaling related gene (HES1, DLL4) and the tight junction proteins genes (ZO-1, OCLN) expressions in HAEC were downregulated in concentration and time-course dependent manner by the exposure to UFP. Conclusion: The UFP exposure affected GVB homeostasis and increased endothelial permeability. This finding supports the link between ambient air pollutant exposure to the impairment in the gastrointestinal system.

POSSIBILITY TO REDUCE THROMBOCYTOPENIA AFTER CHEMORADIOTHERAPY IN ONCOLOGICAL PATIENTS

2017 ◽  
Vol 63 (3) ◽  
pp. 466-469
Author(s):  
Luiza Korytova ◽  
Aleksey Meshechkin ◽  
Oleg Korytov ◽  
V. Krasnikova
Keyword(s):  
Combined Treatment ◽  
Treated Group ◽  
Median Number ◽  
Blood Analysis ◽  
Control Group ◽  
Level Control ◽  
Normal Range ◽  
Oncological Patients ◽  
Level Increase ◽  
And Control

Objective was to establish efficiency of sodium nucleospermat in correcting thrombocytopenia after chemoradiotherapy in oncological patients. Methods and materials. The study included data on 32 patients that had undergone combined treatment from January till May 2016. After detecting thrombocytopenia patients were randomized into two groups (16 patients in each): treated group, where patients received sodium nucleospermat, and control group, where sodium nucleospermat was not used. Thrombocyte level control was done on 5th, 10th and 15th day after treatment was over. Results and discussion. All 16 patients showed positive dynamics in increasing thrombocyte level after Sodium nucleospermat injection course was finished. This was proven by first (5th day) blood analysis. On average thrombocyte level after sodium nucleospermat treatment has risen to normal, at 161х109/1. Only 3 patients from this group had to pause radiotherapy for 5 days. Control group patients, which did not receive sodium nucleospermat, showed evidence of thrombocyte level recovery by 10th day only. On average thrombocyte level increase was insignificant, and median number was 111*109/l. Low thrombocyte level was main reason to pause radiotherapy for 11 (69%) patients in control group. Conclusion. Sodium nucleospermat allowed raising thrombocyte level to the lower normal range, which surpassed by 40%-50% in control group patients. Use of sodium nucleospermat did not show any cases of allergic reactions, toxicity or complications in oncological patients.

scholarly journals Effects of remote ischemic conditioning on microcirculatory alterations in patients with sepsis: a single-arm clinical trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Inga Kiudulaite ◽  
Egle Belousoviene ◽  
Astra Vitkauskiene ◽  
Andrius Pranskunas
Keyword(s):  
Dark Field ◽  
Historical Control ◽  
Flow Index ◽  
Control Group ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Sublingual Microcirculation ◽  
Link Type ◽  
Microcirculatory Flow ◽  
Tertiary Teaching

Abstract Background Remote ischemic conditioning (RIC) is a promising technique that may protect organs and tissues from the effects of additional ischemic episodes. However, the therapeutic efficacy of RIC in humans with sepsis remains unknown. We hypothesized that RIC might improve sublingual microcirculation in patients with sepsis. Methods This prospective single-arm trial was performed in a mixed ICU at a tertiary teaching hospital. We included patients with sepsis or septic shock within 24 h of ICU admission. The RIC procedure comprised 3 cycles of brachial cuff inflation to 200 mmHg for 5 min followed by deflation to 0 mmHg for another 5 min. The procedure took 30 min. RIC was performed at the time of study inclusion and repeated after 12 and 24 h. Sublingual microcirculatory measurements were obtained before and after each RIC procedure using a Cytocam®-incident dark-field (IDF) device (Braedius Medical, Huizen, The Netherlands). The microcirculatory data were compared with a historical control. Data are reported as the medians along with the 25th and 75th percentiles. Results Twenty-six septic patients with a median age of 65 (57–81) years were enrolled in this study. The median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at admission were 20 (13–23) and 10 (9–12), respectively. All patients were receiving vasopressors. After the 1st RIC procedure, the microvascular flow index (MFI) and the proportion of perfused vessels (PPV) among small vessels were significantly higher than before the procedure, with pre- and post-treatment values of 2.17 (1.81–2.69) and 2.59 (2.21–2.83), respectively, for MFI (p = 0.003) and 87.9 (82.4–93.8) and 92.5 (87.9–96.1) %, respectively, for PPV (p = 0.026). This result was confirmed by comparison with a historical control group. We found no change in microcirculatory flow or density parameters during repeated RIC after 12 h and 24 h. Conclusion In patients with sepsis, the first remote ischemic conditioning procedure improved microcirculatory flow, whereas later procedures did not affect sublingual microcirculation. Trial registration NCT04644926, http://www.clinicaltrials.gov. Date of registration: 25 November 2020. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04644926.

scholarly journals Polycystin-2 Activity Is Controlled by Transcriptional Coactivator with PDZ Binding Motif and PALS1-associated Tight Junction Protein

2010 ◽  
Vol 285 (44) ◽  
pp. 33584-33588 ◽  
Author(s):  
Kerstin Duning ◽  
Deike Rosenbusch ◽  
Marc A. Schlüter ◽  
Yuemin Tian ◽  
Karl Kunzelmann ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junction Protein ◽  
Binding Motif ◽  
Transcriptional Coactivator ◽  
Junction Protein

scholarly journals Endothelial-specific insulin receptor substrate-1 overexpression worsens neonatal hypoxic-ischemic brain injury via mTOR-mediated tight junction disassembly

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi-Fang Tu ◽  
Si-Tse Jiang ◽  
Chi-Wu Chiang ◽  
Li-Ching Chen ◽  
Chao-Ching Huang
Keyword(s):  
Endothelial Cells ◽  
Brain Injury ◽  
Tight Junction ◽  
Insulin Receptor ◽  
Vascular Endothelial Cells ◽  
Tight Junction Protein ◽  
Insulin Receptor Substrate ◽  
Vascular Endothelial ◽  
Transgenic Rats ◽  
Junction Protein

AbstractHypoxic-ischemic (HI) encephalopathy is the major cause of mortality and disability in newborns. The neurovascular unit is a major target of acute and chronic brain injury, and therapies that protect simultaneously both neurons and vascular endothelial cells from neonatal HI injury are in demand. Insulin receptors and its key downstream molecule-insulin receptor substrate −1 (IRS-1) are potential neuroprotective targets and expressed both in neuron and endothelial cells. To investigate whether IRS-1 can act similarly in neurons and vascular endothelial cells in protecting neurovascular units and brain form HI injury, we found that neuron-specific IRS-1 transgenic rats showed reduced neurovascular injury and infarct volumes, whereas endothelial-specific IRS-1 transgenic rats showed increased blood-brain barrier (BBB) disruption and exaggerated neurovascular injury after neonatal HI brain injury. Endothelial-specific IRS-1 overexpression increased vascular permeability and disassembled the tight junction protein (zonula occludens-1) complex. Inhibition of mammalian target of rapamycin (mTOR) by rapamycin preserved tight junction proteins and attenuated BBB leakage and neuronal apoptosis after HI in the endothelial-specific IRS-1 transgenic pups. Together, our findings suggested that neuronal and endothelial IRS-1 had opposite effects on the neurovascular integrity and damage after neonatal HI brain injury and that endothelial IRS-1 worsens neurovascular integrity after HI via mTOR-mediated tight junction protein disassembly.

The Tight Junction Protein Cingulin Regulates Gene Expression and RhoA Signaling

2009 ◽  
Vol 1165 (1) ◽  
pp. 88-98 ◽  
Author(s):  
Sandra Citi ◽  
Serge Paschoud ◽  
Pamela Pulimeno ◽  
Francesco Timolati ◽  
Fabrizio De Robertis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Protein ◽  
Junction Protein ◽  
Rhoa Signaling
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