Spelling suggestions: "subject:"ischemia reperfusion injury"" "subject:"lschemia reperfusion injury""
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MicroRNA Regulation of Neutrophil FunctionTheodore G. Naef (5929721) 16 January 2019 (has links)
Neutrophils are significant players in both acute and chronic inflammatory conditions, and function in infectious and autoimmune ailments. MicroRNAs regulate homeostasis in health and disease by fine tuning the expression of a network of genes through post transcriptional regulation. Many microRNAs are expressed in restricted tissues, regulated by physiological conditions such as stress and disease, and are emerging as mediators for intercellular communication that shape the tissue environments. MicroRNA profiles have been recently utilized as biomarkers for diagnosis and prognostic purposes for their stability in plasma and significant correlation with the disease progress. In addition, several microRNAs are in clinical trials for infectious diseases, cardiovascular disorders and cancer. As for neutrophil biology, microRNAs that regulate hematopoiesis and neutrophil development are well known. However, only a few microRNAs are characterized in the context of neutrophil migration and activation by loss of function studies either in mice or in cell culture. In this work we characterize the role of total microRNA regulation on neutrophil function through whole body and neutrophil specific Dicer1 knockout, and identify a microRNA regulator of neutrophil motility. MiR-722 downregulates the transcript level of rac2 through binding to a seed match in the rac2 3'UTR. Furthermore, miR-722 over-expressing larvae display improved outcomes in both sterile and bacterial systemic models. Finally, the miR-722 mimics protect zebrafish from lethal LPS challenge, providing evidence and mechanism of an anti-inflammatory microRNA that restrains detrimental systemic inflammation. We further investigated the role of the inflammatory response in an ischemia-reperfusion model. Extensive future work is required, especially in animal models, to illustrate the pivotal and complex microRNA mediated regulatory network in neutrophils, which is expected to provide the foundation for highly selective microRNA based therapy to control neutrophil behavior in infection and inflammatory disorders.
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Short-term Calorie Restriction Improves Post-ischemic Recovery in the Spontaneously Hypertensive RatLozyk, Mira D Unknown Date
No description available.
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Evaluation of Pulmonary Edema: Stereological versus Gravimetrical AnalysisFehrenbach, Antonia, Fehrenbach, Heinz, Wittwer, Thorsten, Ochs, Matthias, Wahlers, Thorsten, Richter, Joachim 12 February 2014 (has links) (PDF)
Assessment of lung edema by gravimetrical analysis is a standard method to evaluate the severity of experimentally induced ischemia/reperfusion (IR) injury. The aim of this study was to compare gravimetrical assessment of pulmonary edema with a stereological approach which allows for qualitative and quantitative distinction between intravascular and edematous fluids by light microscopy. Eight experimental groups which differed in mode of preservation, ischemic storage and pharmacological treatments were studied in an extracorporeal rat lung model. Analysis of the pooled data showed that the wet/dry ratio values mainly reflected the amount of intra-alveolar edema (rs = 0.442; p = 0.0057) but only stereological assessment of edema formation revealed differences depending on the treatment used. Only stereological data correlated significantly with oxygen tension measured at the end of reperfusion (rs = –0.530; p = 0.0009). We conclude that gravimetry is of minor functional importance compared to assessment by stereological methods which prove to be a reliable and efficient tool for the evaluation of IR injury in the different experimental settings. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Role volných kyslíkových radikálů v ischemicko-reperfuzním poškození plic při plicní transplantaci a možnosti prevence radikálového poškození / Ischemia-reperfusion injury in lungs after transplantation and the role of radical oxygen speciesMrázková, Hana January 2017 (has links)
Keywords: Lung Tx, EVLP, NHBD, IR injury, ROS, hypercapnia, gender differences This dissertation thesis deals with a very topical issue of the lack of donor organs for lung transplants. As with other organs, the number of patients on waiting lists in terminal stages of their diseases is also constantly rising but there is not an adequate increase in donor organs. We focused our experimental work on the development of research concerning the solution which is most successful in a long-term perspective, i.e. organ transplants from non- heart-beating donors (NHBDs), in an ex vivo lung transplant protocol (EVLP) on an animal model (Wistar rats). This is a method which is clinically established worldwide (in the Czech Republic only experimentally) and is constantly subject to further research. Based on earlier studies, we focused the first experimental part of this work on the potential protective effect of hypercapnic ventilation on ischemia-reperfusion (IR) lung injury in EVLP. The study proved that the hypercapnic ventilation has a protective effect on the generation of reactive oxygen species (ROS) in IR lung injury, but only when used in the period of reperfusion. In the second experimental study, we followed up a very topical issue of the effect of gender on IR lung injury in EVLP in...
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Réparation de l'épithélium tubulaire après agression rénale aiguë. Etude du programme cellulaire et modifications épigénétiques / Tubular epithelium repair after acute kidney injury. Cellular reprogramming & epigenetics modificationsBataille, Aurélien 28 October 2016 (has links)
L’insuffisance rénale aiguë (IRA) est une dysfonction d’organe fréquente. Alors que la fonction rénale récupère le plus souvent, on sait depuis 2009 que le pronostic rénal est malgré tout engagé à long terme. L’objectif de ce travail est d’étudier les mécanismes de réparation pathologique de l’épithélium tubulaire afin de mieux comprendre les conséquences à long terme d’un épisode d’IRA.Le parcours des patients après IRA a été transposé dans un modèle à deux agressions (souris C57Bl6/J) : ischémie-reperfusion rénale, suivie à distance par l’administration continue d’angiotensine 2. L’agression aiguë a été calibrée pour obtenir une récupération fonctionnelle et une histologique (microarchitecture normale à la fin du processus de réparation). La fibrose rénale sous angiotensine 2 était plus importante après un antécédent de nécrose tubulaire ischémique résolutive. En isolant les cellules du tube proximal différenciées, une reprogrammation durable du métabolisme et une probable compartimentalisation de la fibrogénèse ont été mises en évidence.L’hypothèse d’un mécanisme épigénétique, faisant le lien entre ischémie-reperfusion et fibrose à distance, a été explorée. Des modifications d’acétylation des histones dans les cellules tubulaires ont été constatées sur des biopsies des greffons humains en post-IRA. Ces modifications ont été reproduites chez la souris et modélisées in vitro après hypoxie-réoxygénation sur une culture primaire de cellules tubulaires. L’acétylation du locus du gène du micro-ARN miR21, dont les cibles sont impliquées dans la progression de la fibrose, est augmentée après ischémie-reperfusion et associée à son induction. / Acute kidney injury (AKI) is a frequent organ dysfunction. While renal function generally recovers, it has been shown since 2009 that AKI carries a poor long-term renal prognosis. The objective of this study was to investigate the maladaptive repair of the tubular epithelium in order to better understand the long-term consequences of AKI. The course of patients after AKI was transposed into a two-hit animal model (C57Bl6/J mice): renal ischemia-reperfusion, followed by continuous administration of angiotensin 2. AKI was calibrated so as to obtain full functional recovery and normal microarchitecture after ischemic tubular necrosis. There was greater renal fibrosis under angiotensin 2 after a history of resolving ischemic tubular necrosis. By isolating differentiated proximal tubular cells, sustained metabolism reprogramming and compartmentalization of fibrogenesis were highlighted. The hypothesis of an underlying epigenetic mechanism, linking ischemia-reperfusion to fibrosis, was explored. Histone post-translational modifications (H3K18 acetylation) in tubular cells were found in human graft biopsies. These changes were reproduced in mice and modeled in vitro after hypoxia-reoxygenation on a primary culture of tubular cells. Histone acetylation peaked at the locus of the miR21 microRNA gene, whose targets are involved in the progression of fibrosis, and was implicated in miR21 expression following our model of AKI.
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Potential neuroprotective effects of fermented rooibos herbal tea in a rat model of ischemic brain injuryAkinrinmade, Olusiji Alex January 2015 (has links)
Magister Scientiae (Medical Bioscience) - MSc(MBS) / Stroke is the third leading cause of death in South Africa, killing about 240 people a day and leaving survivors with residual disabilities. There is no clinically approved neuroprotective agent for stroke at the moment but the consumption of plant polyphenols has been suggested to offer neuroprotection against stroke and other neurodegenerative diseases. In this study, we investigated the effects of long term consumption of fermented rooibos herbal tea (FRHT) on ischemia reperfusion brain injury (I-RBI) in rats. Male adult Wistar rats were fed FRHT ad libitum for 7 weeks prior to the induction of ischemic injury by the transient bilateral occlusion of the common carotid arteries (BCCAO) for 20 minutes followed by 24 hours, 4 and 7 days of reperfusion respectively. Rats were then evaluated for neurologic deficits
before sacrifice and brains harvested for assessment of brain oedema, blood-brain-barrier (BBB) integrity through Evans blue extravasation (EBE), immunohistochemical studies of apoptosis and lipid peroxidation. Oxygen radical antioxidant capacity and ferric reducing antioxidant power assays were also conducted to assess total antioxidant capacity after ischemia-reperfusion injury. Notably, the long term consumption of fermented rooibos herbal tea prevented brain oedema by reducing cerebral swelling induced by I-RBI. We also observed that fermented rooibos herbal tea offered neuroprotection against damage to the
BBB and delayed neuronal death associated with BCCAO as fewer apoptotic cells were identified 7 days post BCCAO reperfusion. Significantly reduced levels of lipid peroxidation and increased levels of total antioxidant capacity were also observed in brain specimens of rats treated with FRHT. Rats treated with FRHT also showed improved neurologic outcomes when compared with the untreated animals. Our results show that FRHT has potent antioxidant and anti-inflammatory properties which can provide neuroprotective effects against neuronal cell loss, cerebral swelling, BBB disruption, lipid peroxidation and neurologic deficits following I-RBI. The use of FRHT is therefore highly recommended for patients with conditions that predispose them to stroke.
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Role of TLRs, Hippo-YAP1 Signaling, and microRNAs in Cardiac Repair and Regeneration of Damaged myocardium During Ischemic InjuryWang, Xiaohui 01 August 2017 (has links) (PDF)
Cardiovascular disease is a leading cause of death in the United States. Toll-like receptor (TLR)-mediated pathways have been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury. We and others have shown that PI3K/Akt signaling is involved in regulating cellular survival and protecting the myocardium from I/R induced injury. In this dissertation, we provide compelling evidence that miR-125b serves to “fine tune” TLR mediated NF-kB responses by repressing TNF-a and TRAF6 expression. We constructed lentiviral expressing miR-125b, delivered it into the myocardium. The data showed that delivery of lentivirus expressing miR-125b significantly reduces myocardial infarct size and improves cardiac function in I/R hearts. Mechanistic studies demonstrated that miR-125b negatively regulates TLR mediated NF-kB activation pathway by repressing TNF-a and TRAF6 expression in the myocardium.
We also observed that transfection of the myocardium with lentivirus expressing miR-214 markedly attenuates I/R induced myocardial infarct size and cardiac dysfunction. We demonstrated that miR-214 activates PI3K/Akt signaling by targeting PTEN expression in the myocardium.
We also investigated the role of TLR3 in neonatal heart repair and regeneration following myocardial infarction (MI). Wild type (WT) neonatal mice showed fully cardiac functional recovery and small infarct size, while TLR3 deficient mice exhibited impaired cardiac functional recovery and large infarct area after MI. Poly (I:C), a TLR3 ligand, administration significantly enhances glycolysis, YAP1 activation and the proliferation of WT neonatal cardiomyocytes. 2-deoxyglucose (2-DG), a glycolysis inhibitor treatment abolished cardiac functional recovery and YAP1 activation in neonatal mice after MI. In vitro either inhibition of glycolysis by 2-DG or inhibition of YAP1 activation prevents Poly (I:C) induced YAP1 activation and neonatal cardiomyocyte proliferation. Importantly, YAP1 activation increases miR-152 expression, leading to cardiomyocyte proliferation through suppression P27kip1 and DNMT1 expression.
We conclude that microRNAs play an important role in TLR modulation induced protection against myocardial I/R injury by increasing the activation of PI3K/Akt signaling pathway, decreasing TLR/NF-kB mediated inflammatory response, and suppressing activation of apoptotic signaling following myocardial I/R injury.
In addition, TLR3 is an essential for neonatal heart repair and regeneration after myocardial infarction. TLR3 modulation could be a novel strategy for heart regeneration and repair.
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Cardiac Na/K-ATPase in Ischemia-Reperfusion Injury and CardioprotectionDuan, Qiming 22 July 2014 (has links)
No description available.
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The Role of Innate Immune Cells in the Prediction of Early Renal Allograft Injury Following Kidney TransplantationJahn, Nora, Sack, Ulrich, Stehr, Sebastian, Vöelker, Maria Theresa, Laudi, Sven, Seehofer, Daniel, Atay, Selim, Zgoura, Panagiota, Viebahn, Richard, Boldt, Andreas, Hau, Hans-Michael 31 July 2024 (has links)
Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation. The main outcome parameter was the occurrence of eRGI and other outcome parameters associated with graft function/outcome. eRGI was defined as graft-related complications and clinical signs of renal IRI (ischemia reperfusion injury), such as acute tubular necrosis (ATN), delayed graft function (DGF), initial nonfunction (INF) and graft rejection within 3 months following KT. Typical innate immune cells including neutrophils, natural killer (NK) cells, monocytes, basophils and dendritic cells (myeloid, plasmacytoid) were measured in all patients in peripheral blood at day 0, 1, 3, 7 and 10 after the transplantation. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for eRGI. Cutoff levels were calculated with the Youden index. Significant diagnostic immunological cutoffs and other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 50 included patients, 23 patients developed eRGI. Mean levels of neutrophils and monocytes were significantly higher on most days in the eRGI group compared to the non-eRGI group after transplantation, whereas a significant decrease in NK cell count, basophil levels and DC counts could be found between baseline and postoperative course. ROC analysis indicated that monocytes levels on POD 7 (AUC: 0.91) and NK cell levels on POD 7 (AUC: 0.92) were highly predictive for eRGI after KT. Multivariable analysis identified recipient age (OR 1.53 (95% CI: 1.003–2.350), p = 0.040), recipient body mass index > 25 kg/m2 (OR 5.6 (95% CI: 1.36–23.9), p = 0.015), recipient cardiovascular disease (OR 8.17 (95% CI: 1.28–52.16), p = 0.026), donor age (OR 1.068 (95% CI: 1.011–1.128), p = 0.027), <0.010), deceased-donor transplantation (OR 2.18 (95% CI: 1.091–4.112), p = 0.027) and cold ischemia time (CIT) of the renal graft (OR 1.005 (95% CI: 1.001–1.01), p = 0.019) as clinically relevant prognostic factors associated with increased eRGI following KT. Further, neutrophils > 9.4 × 103/μL on POD 7 (OR 16.1 (95% CI: 1.31–195.6), p = 0.031), monocytes > 1150 cells/ul on POD 7 (OR 7.81 (95% CI: 1.97–63.18), p = 0.048), NK cells < 125 cells/μL on POD 3 (OR 6.97 (95% CI: 3.81–12.7), p < 0.01), basophils < 18.1 cells/μL on POD 10 (OR 3.45 (95% CI: 1.37–12.3), p = 0.02) and mDC < 4.7 cells/μL on POD 7 (OR 11.68 (95% CI: 1.85–73.4), p < 0.01) were revealed as independent biochemical predictive variables for eRGI after KT. Conclusions: We show that the combined measurement of immunological innate variables (NK cells and monocytes on POD 7) and specific clinical factors such as prolonged CIT, increased donor and recipient age and morbidity together with deceased-donor transplantation were significant and specific predictors of eRGI following KT. We suggest that intensified monitoring of these parameters might be a helpful clinical tool in identifying patients at a higher risk of postoperative complication after KT and may therefore help to detect and—by diligent clinical management—even prevent deteriorated outcome due to IRI and eRGI after KT.
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PATHOGENIC ROLE OF PHOSPHODIESTERASE TYPE 5 UPREGULATION IN CARDIAC ISCHEMIA/REPERFUSION INJURYHobbs, Daniel 13 July 2010 (has links)
Phosphodiesterase Type 5 (PDE5) inhibitors are cardioprotective against ischemia/reperfusion (I/R) injury. However, it remains uncertain if I/R affects PDE5. We hypothesized that generation of reactive oxygen species (ROS) during I/R leads to upregulation of PDE5, which contributes to pathological changes following acute myocardial infarction (AMI). Adult male ICR mice were subjected to 30 minutes of in vivo or ex vivo I/R. To examine the role of ROS, a subset of hearts were perfused with 100 µM hydrogen peroxide (H2O2). Expression and activity of PDE5, pPDE5, and cGMP-dependent protein kinase (PKG) were measured by Western blots and spectrophotometric assay. The results show that ischemia and I/R significantly increased expression of PDE5. H2O2 had no effect on PDE5 expression and activity but significantly increased PKG activity. We conclude that acute cardiac ischemia or I/R upregulate PDE5 independent of oxidant stress in the heart.
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