The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

Gu, Tingting; Just, Jesper; Stenz, Katrine Tang; Yan, Yan; Sieljacks, Peter; Wang, Jakob; Groennebaek, Thomas; Jakobsgaard, Jesper Emil; Rindom, Emil; Herskind, Jon; Gravholt, Anders; Lassen, Thomas Ravn; Jørgensen, Mathias; Bæk, Rikke; Gutiérrez‐Jiménez, Eugenio; Iversen, Nina; Rasmussen, Peter Mondrup; Nyengaard, Jens Randel; Jørgensen, Maléne Møller; Paoli, Frank Vincenzo de; Bøtker, Hans Erik; Kjems, Jørgen; Vissing, Kristian; Drasbek, Kim Ryun

doi:10.3390/ijms23063334

Cited by 13 publications

(16 citation statements)

References 100 publications

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“…Tissue oxygenation can be measured using several techniques, including near-infrared spectroscopy, white light spectroscopy, optical/fluorescence-based oxygen monitoring, and reflectance spectroscopy imaging. These techniques have been used to monitor the oxygenation of the central nervous system in animal models (11, 16, 30, 37). However, these devices are expensive and may not be affordable in general labs.…”

Section: Discussionmentioning

confidence: 99%

Acute hyperoxia improves spinal cord oxygenation and circulatory function following cervical spinal cord injury in the rat

Lin,

Lee

2023

Preprint

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Spinal cord injury is associated with spinal vascular disruptions that result in spinal ischemia and tissue hypoxia. This study evaluated the therapeutic efficacy of normobaric hyperoxia on spinal cord oxygenation and circulatory function at the acute stage of cervical spinal cord injury. Adult male Sprague Dawley rats underwent dorsal cervical laminectomy or cervical spinal cord contusion. At 1 to 2 days after spinal surgery, spinal cord oxygenation was monitored in anesthetized and spontaneously breathing rats via the optical recording of oxygen sensor foils placed on the cervical spinal cord and pulse oximetry. The arterial blood pressure, heart rate, blood gases, and peripheral oxyhemoglobin saturation were also measured under hyperoxic (50% O2) and normoxic (21% O2) breathing. The results showed that contused animals had a significantly lower spinal cord oxygenation level than uninjured animals during normoxia. Cervical spinal cord contusion also significantly reduced peripheral oxyhemoglobin saturation, arterial oxygen partial pressure, and mean arterial blood pressure. Notably, the spinal oxygenation of contused rats could be improved to a level comparable to uninjured animals under hyperoxia. Furthermore, acute hyperoxia could elevate blood pressure, arterial oxygen partial pressure, and peripheral oxyhemoglobin saturation. These results suggest that normobaric hyperoxia can significantly improve spinal cord oxygenation and circulatory function during acute cervical spinal cord injury. We propose that adjuvant normobaric hyperoxia combined with other hemodynamic optimization strategies may prevent secondary damage after spinal cord injury and improve functional recovery.

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Section: Discussionmentioning

confidence: 99%

Acute hyperoxia improves spinal cord oxygenation and circulatory function following cervical spinal cord injury in the rat

Lin,

Lee

2023

Preprint

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“…As research has progressed, several animal studies have confirmed that RIPostC can improve the prognosis of cerebrovascular disease and can protect the brain from ischemic injury ( 13 , 36 , 37 ). Several potential mechanisms of action also explain the cerebroprotective effects of RIPostC, and studies have shown that RIPostC may mediate neuroprotection through glucagon-like-peptide-1 receptor (GLP-1R) activation ( 38 ) and may also exert cerebroprotective effects by mediating the release of extracellular vesicles (EVs) in the plasma ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Cerebral protection by remote ischemic post-conditioning in patients with ischemic stroke: A systematic review and meta-analysis of randomized controlled trials

et al. 2022

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BackgroundThere is evidence that remote limb ischemic postconditioning (RIPostC) can reduce ischemia-reperfusion injury (IRI) and improve the prognosis of patients with ischemic stroke. However, so far, only few relevant clinical studies have been conducted. Therefore, we carried out a meta-analysis of eligible randomized controlled trials to compare the RIPostC group with a control group (no intervention or sham surgery) in patients with ischemic stroke.MethodsFour English-language publication databases, PubMed, Cochrane, Embase, and Web of Science, were systematically searched up to March 2022. The data were analyzed using Review Manager fixed-effects and random-effects models.ResultsA total of 12 studies were included, and 11 of those were analyzed quantitatively. Compared to controls, The RIPostC group showed significantly reduced NIHHS scores in patients with ischemic stroke, (MD: −1.09, 95% confidence interval [CI]: −1.60, −0.57, P < 0.0001) and improved patients' Montreal Cognitive Assessment (MoCA) scores, (MD: 1.89, 95% CI: 0.78, 3.00, P = 0.0009), Our results showed that RIPostC is safe, (RR = 0.81, 95%CI: 0.61, 1.08, P = 0.15).ConclusionOur meta-analysis showed that RIPostC is safe and effective and has a positive cerebral protective effect in patients with ischemic stroke, which is safe and effective, and future large-sample, multicenter trials are needed to validate the cerebral protective effect of RIPostC.

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“…95 Also, use of human plasma, platelets and myocardial tissue for in vitro studies of cardioprotective effects and signalling is useful before embarking on clinical studies in patients. [96][97][98][99][100] Exosomes are released during remote ischaemic conditioning, [101][102][103] may be carriers of cardioprotective signals 102,104 and can possibly be exploited as therapeutic vehicles in the future. 105 Very recently, pretreatment with a sodium-glucose transport inhibitor reduced infarct size in isolated perfused mouse hearts, 106 and this approach seems worth to be followed up with more translational approaches.…”

Section: Perspective -The Need For Pragmatism and Innovationmentioning

confidence: 99%

Cardioprotection and its Translation: A Need for New Paradigms? Or for New Pragmatism? An Opinionated Retro- and Perspective

Heusch

2023

J Cardiovasc Pharmacol Ther

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The dawn of cardioprotection by infarct size reduction originated from the idea to favourably alter the oxygen demand–supply balance of the ischaemic/infarcting myocardium by reducing the contractile determinants of its oxygen consumption. This idea is probably not correct, since the ischaemic/infarcting myocardium does not contract anyway. None of the successful initial preclinical attempts of infarct size reduction translated into clinical practice, except for timely reperfusion which has become and still is the backbone of all clinical infarct therapy up today. The idea of cardioprotection gained momentum again with the recognition of ischaemic conditioning, and a myriad of preclinical studies have identified molecules and mechanisms of such self-defence mechanism. Although there are positive clinical proof-of-concept studies, ischaemic conditioning strategies and drugs related to its signal transduction have not translated into clinical practice. We are currently trying to understand the obstacles to translation from successful preclinical studies on cardioprotection to clinical practice, but are also waiting for an innovative mechanistic breakthrough.

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The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

Cited by 13 publications

References 100 publications

Acute hyperoxia improves spinal cord oxygenation and circulatory function following cervical spinal cord injury in the rat

Acute hyperoxia improves spinal cord oxygenation and circulatory function following cervical spinal cord injury in the rat

Cerebral protection by remote ischemic post-conditioning in patients with ischemic stroke: A systematic review and meta-analysis of randomized controlled trials

Cardioprotection and its Translation: A Need for New Paradigms? Or for New Pragmatism? An Opinionated Retro- and Perspective

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