Postconditioning fails to prevent radial artery endothelial dysfunction induced by ischemia and reperfusion: evidence from a human in vivo study

2006 ◽  
Vol 84 (6) ◽  
pp. 611-615 ◽  
Author(s):  
Saverio Dragoni ◽  
Giuseppe Di Stolfo ◽  
Silvia Sicuro ◽  
Monica Lisi ◽  
John D. Parker ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Radial Artery ◽  
Tissue Damage ◽  
Animal Studies ◽  
In Vivo Model ◽  
Ischemia And Reperfusion ◽  
Ischemic Tissue ◽  
Before And After ◽  
Dependent Flow

Animal studies have shown that, as compared with unrestricted reperfusion, exposure to brief periods of controlled ischemia (postconditioning) at the end of a prolonged ischemia reduces the extent of tissue damage. We set out to test whether postconditioning can prevent endothelial dysfunction induced by ischemia and reperfusion in a human in vivo model. Ten healthy young non-smoking volunteers were enrolled in this cross-over, controlled, investigator-blinded study. Subjects were exposed to 15 min of forearm ischemia followed by either unrestricted reperfusion or postconditioning (3 periods of 20 s of ischemia separated by 10 s of reperfusion). Endothelium-dependent flow-mediated dilation (FMD) was measured at the level of the radial artery before and after ischemia (with or without postconditioning). Forearm ischemia blunted FMD in both study visits (unrestricted reperfusion visit: before ischemia, 7.7% ± 1.3%; after ischemia, 2.5% ± 1.4%; and postconditioning visit: before, 7.3% ± 1.2%; after, 2.6 ± 1.6%; P < 0.05 for both, P = not significant (NS) between visits). In contrast with data from animal studies, postconditioning (20 s ischemia – 10 s reperfusion repeated 3 times) does not limit post-ischemic endothelial dysfunction in this human in vivo model. Further human studies are necessary to evaluate other reperfusion protocols in an attempt to limit post-ischemic tissue damage.

Effects of the SOD mimetic, M40403, on prostaglandin production in an in vivo model of ischemia and reperfusion in rat heart

2003 ◽  
Vol 52 (0) ◽  
pp. s23-s24 ◽  
Author(s):  
C. Marzocca ◽  
A. Vannacci ◽  
S. Cuzzocrea ◽  
D. Salvemini ◽  
P. F. Mannaioni ◽  
...  
Keyword(s):  
Rat Heart ◽  
In Vivo Model ◽  
Ischemia And Reperfusion ◽  
Prostaglandin Production

scholarly journals Plasticity after cortical stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits

2020 ◽  
Author(s):  
William A Zeiger ◽  
Máté Marosi ◽  
Satvir Saggi ◽  
Natalie Noble ◽  
Isa Samad ◽  
...  
Keyword(s):  
Animal Studies ◽  
Structural Changes ◽  
Recovery Of Function ◽  
Definitive Evidence ◽  
Before And After ◽  
Maladaptive Plasticity ◽  
Adaptive Circuit ◽  
Evoked Activity ◽  
Sensory Evoked

AbstractFunctional recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. This “remapping” hypothesis is based on human brain mapping studies showing apparent reorganization of cortical sensorimotor maps and animal studies documenting molecular and structural changes that could support circuit rewiring. However, definitive evidence of remapping is lacking, and other studies have suggested that maladaptive plasticity mechanisms, such as enhanced inhibition in peri-infarct cortex, might actually limit plasticity after stroke. Here we sought to directly test whether neurons can change their response selectivity after a stroke that destroys a single barrel (C1) within mouse primary somatosensory cortex. Using multimodal in vivo imaging approaches, including two-photon calcium imaging to longitudinally record sensory-evoked activity in peri-infarct cortex before and after stroke, we found no evidence to support the remapping hypothesis. In an attempt to promote plasticity via rehabilitation, we also tested the effects of forced use therapy by plucking all whiskers except the C1 whisker. Again, we failed to detect an increase in the number of C1 whisker-responsive neurons in surrounding barrels even 2 months after stroke. Instead, we found that forced use therapy potentiated sensory-evoked responses in a pool of surviving neurons that were already C1 whisker responsive by significantly increasing the reliability of their responses. Together, our results argue against the long-held theory of functional remapping after stroke, but support a plausible circuit-based mechanism for how rehabilitation may improve recovery of function.

scholarly journals Resistance of Optogenetically Evoked Motor Function to Global Ischemia and Reperfusion in Mouse in Vivo

2013 ◽  
Vol 33 (8) ◽  
pp. 1148-1152 ◽  
Author(s):  
Yicheng Xie ◽  
Shangbin Chen ◽  
Eitan Anenberg ◽  
Timothy H Murphy
Keyword(s):  
Sensory Processing ◽  
Muscle Activity ◽  
Motor Output ◽  
Global Ischemia ◽  
Differential Sensitivity ◽  
In Vivo Model ◽  
Ischemia And Reperfusion ◽  
Motor Systems ◽  
Minute Period

Recently we have shown that despite reperfusion, sensory processing exhibits persistent deficits after global ischemia in a mouse in vivo model. We now address how motor output, specifically cortically evoked muscle activity, stimulated by channelrhodopsin-2 is affected by global ischemia and reperfusion. We find that the light-based optogenetic motor map recovers to 80% within an hour. Moreover, motor output recovers relatively faster and more completely than the sensory processing after 5-minute period of global ischemia. Our results suggest a differential sensitivity of sensory and motor systems to the effects of global ischemia and reperfusion that may have implications for rehabilitation.

scholarly journals Plectasin Shows Intracellular Activity against Staphylococcus aureus in Human THP-1 Monocytes and in a Mouse Peritonitis Model

2009 ◽  
Vol 53 (11) ◽  
pp. 4801-4808 ◽  
Author(s):  
Karoline Sidelmann Brinch ◽  
Anne Sandberg ◽  
Pierre Baudoux ◽  
Françoise Van Bambeke ◽  
Paul M. Tulkens ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Animal Studies ◽  
Kinetic Studies ◽  
Response To Therapy ◽  
In Vitro Studies ◽  
In Vivo Model ◽  
Intracellular Activity ◽  
Peritonitis Model

ABSTRACT Antimicrobial therapy of infections with Staphylococcus aureus can pose a challenge due to slow response to therapy and recurrence of infection. These treatment difficulties can partly be explained by intracellular survival of staphylococci, which is why the intracellular activity of antistaphylococcal compounds has received increased attention within recent years. The intracellular activity of plectasin, an antimicrobial peptide, against S. aureus was determined both in vitro and in vivo. In vitro studies using THP-1 monocytes showed that some intracellular antibacterial activity of plectasin was maintained (maximal relative efficacy [E max], 1.0- to 1.3-log reduction in CFU) even though efficacy was inferior to that of extracellular killing (E max, >4.5-log CFU reduction). Animal studies included a novel use of the mouse peritonitis model, exploiting extra- and intracellular differentiation assays, and assessment of the correlations between activity and pharmacokinetic (PK) parameters. The intracellular activity of plectasin was in accordance with the in vitro studies, with an E max of a 1.1-log CFU reduction. The parameter most important for activity was fC peak/MIC, where fC peak is the free peak concentration. These findings stress the importance of performing studies of extra- and intracellular activity since these features cannot be predicted from traditional MIC and killing kinetic studies. Application of both the THP-1 and the mouse peritonitis models showed that the in vitro results were similar to findings in the in vivo model with respect to demonstration of intracellular activity. Therefore the in vitro model was a good screening model for intracellular activity. However, animal models should be applied if further information on activity, PK/pharmacodynamic parameters, and optimal dosing regimens is required.

Short ischemia causes endothelial dysfunction in porcine coronary vessels in an in vivo model

2001 ◽  
Vol 71 (1) ◽  
pp. 265-269 ◽  
Author(s):  
Ulf Lockowandt ◽  
Jan Liska ◽  
Anders Franco-Cereceda
Keyword(s):  
Endothelial Dysfunction ◽  
Coronary Vessels ◽  
In Vivo Model

scholarly journals Indolent course of tubulointerstitial disease in a mouse model of subpressor, low-dose nitric oxide synthase inhibition

2008 ◽  
Vol 295 (3) ◽  
pp. F717-F725 ◽  
Author(s):  
Adelina Stoessel ◽  
Alexander Paliege ◽  
Franziska Theilig ◽  
Francesco Addabbo ◽  
Brian Ratliff ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Basement Membrane ◽  
Mouse Model ◽  
Asymmetric Dimethylarginine ◽  
In Vivo Model ◽  
No Production ◽  
Collagen Xviii

Deficiency of nitric oxide (NO) represents a consistent manifestation of endothelial dysfunction (ECD), and the accumulation of asymmetric dimethylarginine occurs early in renal disease. Here, we confirmed in vitro and in vivo the previous finding that a fragment of collagen XVIII, endostatin, was upregulated by chronic inhibition of NO production and sought to support a hypothesis that primary ECD contributes to nephrosclerosis in the absence of other profibrotic factors. To emulate more closely the indolent course of ECD, the study was expanded to an in vivo model with NG-monomethyl-l-arginine(l-NMMA; mimics effects of asymmetric dimethylarginine) administered to mice in the drinking water at subpressor doses of 0.3 and 0.8 mg/ml for 3–6 mo. This resulted in subtle but significant morphological alterations detected in kidneys of mice chronically treated with l-NMMA: 1) consistent perivascular expansion of interstitial matrix components at the inner stripe of the outer medulla and 2) collagen XVIII/endostatin abundance. Ultrastructural abnormalities were detected in l-NMMA-treated mice: 1) increased activity of the interstitial fibroblasts; 2) occasional detachment of endothelial cells from the basement membrane; 3) splitting of the vascular basement membrane; 4) focal fibrosis; and 5) accumulation of lipofuscin by interstitial fibroblasts. Preembedding labeling of microvasculature with anti-CD31 antibodies showed infiltrating leukocytes and agglomerating platelets attaching to the visibly intact or denuded capillaries. Collectively, the data indicate that the mouse model of subpressor chronic administration of l-NMMA is not a robust one (endothelial pathology visible only ultrastructurally), and yet it closely resembles the natural progression of endothelial dysfunction, microvascular abnormalities, and associated tubulointerstitial scarring.

scholarly journals Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2481
Author(s):  
Norah A. Althobaiti ◽  
Farid Menaa ◽  
Aishah E. Albalawi ◽  
Johnathan J. Dalzell ◽  
Neil D. Warnock ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Globodera Pallida ◽  
Model Systems ◽  
In Vivo Model ◽  
Aβ Peptides ◽  
Before And After ◽  
Pre Treatment

Background: Whole transgenic or non-transgenic organism model systems allow the screening of pharmacological compounds for protective actions in Alzheimer’s disease (AD). Aim: In this study, a plant parasitic nematode, Globodera pallida, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. Methods: Fresh second-stage juveniles of G. pallida were used to measure their chemosensory, perform immunocytochemistry on their neurological structures, evaluate their survival rate, measure reactive oxygen species, and determine total oxidized glutathione to reduced glutathione ratio (GSSG/GSH) levels, before and after treatment with 100 µM of various amyloid beta (Aβ) peptides (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16). Wild-type N2 C. elegans (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) G. pallida (unlike Caenorhabditis elegans) assimilates amyloid-β (Aβ) peptides which co-localise with its neurological structures; (ii) pre-treatment with various Aβ isoforms (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16) impairs G. pallida’s chemotaxis to differing extents; (iii) Aβ peptides reduced survival, increased the production of ROS, and increased GSSG/GSH levels in this model; (iv) this unique model can distinguish differences between different treatment concentrations, durations, and modalities, displaying good sensitivity; (v) clinically approved neuroprotective agents were effective in protecting G. pallida from Aβ (1–42) exposure. Taken together, the data indicate that G. pallida is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.

scholarly journals Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice

2021 ◽  
Vol 22 (21) ◽  
pp. 11612
Author(s):  
Junying Xiao ◽  
Na Li ◽  
Shengze Xiao ◽  
Yuzhou Wu ◽  
Hongmei Liu
Keyword(s):  
Endothelial Dysfunction ◽  
Apolipoprotein E ◽  
Animal Studies ◽  
Vascular Inflammation ◽  
Selenium Nanoparticles ◽  
In Vivo Experiments ◽  
Nitric Oxide Level ◽  
Underlying Mechanisms ◽  
Atherosclerosis Prevention

Atherosclerosis and related cardiovascular diseases represent the greatest threats to human health, worldwide. Previous animal studies showed that selenium nanoparticles (SeNPs) and Na2SeO3 might have anti-atherosclerotic activity, but the underlying mechanisms are poorly elucidated. This study compared the anti-atherosclerotic activity of SeNPs stabilized with chitosan (CS-SeNPs) and Na2SeO3 and the related mechanism in a high-fat-diet-fed apolipoprotein E-deficient mouse model of atherosclerosis. The results showed that oral administration of both CS-SeNPs and Na2SeO3 (40 μg Se/kg/day) for 10 weeks significantly reduced atherosclerotic lesions in mouse aortae. Mechanistically, CS-SeNPs and Na2SeO3 not only alleviated vascular endothelial dysfunction, as evidenced by the increase of serum nitric oxide level and the decrease of aortic adhesion molecule expression, but also vascular inflammation, as evidenced by the decrease of macrophage recruitment as well as the expression of proinflammatory molecules. Importantly, these results were replicated within in-vivo experiments on the cultured human endothelial cell line EA.hy926. Overall, CS-SeNPs had a comparable effect with Na2SeO3 but might have more potential in atherosclerosis prevention due to its lower toxicity. Together, these results provide more insights into the mechanisms of selenium against atherosclerosis and further highlight the potential of selenium supplementation as a therapeutic strategy for atherosclerosis.

scholarly journals One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization

2021 ◽  
Author(s):  
Maggie Gu ◽  
Jonathan L. Torres ◽  
Jack Greenhouse ◽  
Shannon Wallace ◽  
Chi-I Chiang ◽  
...  
Keyword(s):  
Single Dose ◽  
Tissue Damage ◽  
Vaccine Candidate ◽  
In Vivo Model ◽  
Single Shot ◽  
Virus Challenge ◽  
Post Immunization ◽  
Viral Loads ◽  
Viral Spread

AbstractA COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.

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