Preclinical Validation of the Therapeutic Potential of Glasgow Oxygen Level Dependent (GOLD) Technology: a Theranostic for Acute Stroke

Deuchar, Graeme A.; Kralingen, Josie C van; Work, Lorraine M.; Santosh, Celestine; Muir, Keith W.; McCabe, Chris; Macrae, I. Mhairi

doi:10.1007/s12975-018-0679-y

Cited by 14 publications

(11 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A PFOB nanoemulsion improved myocardial oxygenation and cardiac function in the isolated working rabbit heart [ 70 ]. Administration of a PFC emulsion reduced infarct size and improved functional recovery after acute ischemic stroke in the rat [ 71 ]. Resuscitation of mice from hemorrhagic shock with a PFOB emulsion was comparable to that achieved with whole blood [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model

İnci

Arni

Çıtak

et al. 2020

Cells

View full text Add to dashboard Cite

Background: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We hypothesized that perfluorocarbon-based oxygen carrier, a novel reconditioning strategy instilled during EVLP would improve graft function. Methods: We utilized perfluorocarbon-based oxygen carrier (PFCOC) during EVLP to recondition and improve lung graft function in a pig model of EVLP and lung transplantation. Lungs were retrieved and stored for 24 h at 4 °C. EVLP was done for 6 h with or without PFCOC. In the transplantation groups, left lung transplantation was done after EVLP with or without PFCOC. Allograft function was assessed by means of pulmonary gas exchange, lung mechanics and vascular pressures, histology and transmission electron microscopy (TEM). Results: In the EVLP only groups, physiological and biochemical markers during the 6-h perfusion period were comparable. However, perfusate lactate potassium levels were lower and ATP levels were higher in the PFCOC group. Radiologic assessment revealed significantly more lung infiltrates in the controls than in the PFCOC group (p = 0.04). In transplantation groups, perfusate glucose consumption was higher in the control group. Lactate levels were significantly lower in the PFCOC group (p = 0.02). Perfusate flavin mononucleotide (FMN) was significantly higher in the controls (p = 0.008). Post-transplant gas exchange was significantly better during the 4-h reperfusion period in the PFCOC group (p = 0.01). Plasma IL-8 and IL-12 levels were significantly lower in the PFCOC group (p = 0.01, p = 0.03, respectively). ATP lung tissue levels at the end of the transplantation were higher and myeloperoxidase (MPO) levels in lung tissue were lower in the PFCOC group compared to the control group. In the PFCOC group, TEM showed better tissue preservation and cellular viability. Conclusion: PFCOC application is safe during EVLP in lungs preserved 24 h at 4 °C. Although this strategy did not significantly affect the EVLP physiology, metabolic markers of the donor quality such as lactate production, glucose consumption, neutrophil infiltration and preservation of mitochondrial function were better in the PFCOC group. Following transplantation, PFCOC resulted in better graft function and TEM showed better tissue preservation, cellular viability and improved gas transport.

show abstract

Section: Discussionmentioning

confidence: 99%

Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model

İnci

Arni

Çıtak

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…At 100% O 2 the transcutaneous oxygen pressure raises from 150 mmHg up to 470 mmHg 14. Moreover, this single dose of oxygen increases the expression of erythropoietin in the serum of patients,1415 increases reactive oxygen species formation followed by an increased production of glutathione 1516. However, it is unknown if NBO promotes S/PC mobilization or modulates cytokine production similar to HBO therapy 41718192021.…”

Section: Introductionmentioning

confidence: 99%

Effect of intermittent hyperoxia on stem cell mobilization and cytokine expression

et al. 2019

View full text Add to dashboard Cite

Introduction Modern medicine has made enormous progress in the past 150 years including the development of vaccines and pharmaceutical therapies. However, to date there is little progress in developing therapies that speed the healing of injured tissues. Hyperbaric oxygen therapy (HBOT) is a FDA approved therapy for non‐healing wounds consisting of daily intermittent doses of elevated partial pressure of oxygen (PO2) above 1520 torr. The hypothetical mechanism is its influence on mobilizing stem cells via cell signaling and gene transcription at effector tissues. Preclinical research showed a regimen of HBOT resulted in mobilization of stem cells and increased vasculogenesis in a wound healing model. Our study sought to determine if partial pressures of oxygen less than 760 torr would also mobilize stem cells. Methods Twelve, 10‐week‐old Sprague Dawley rats were randomly divided into two groups. The treatment group was exposed to a hyperoxic environment with a PO2 = 319 torr. The control group was exposed to room air (PO2 = 159 torr). Treatments were performed 5 days per week for 2 hours daily for a total of 10 treatment days (20 hours). Animals were sacrificed and approximately 8 ml of venous blood was harvested from the inferior vena cava. Red blood cells were lysed and plasma was drawn off and frozen. Remaining cells were prepared for flow cytometry by exposing them to cell surface marker antibodies for CD34+and CD 133+. These cells were then analyzed on a BD LSRII flow cytometer using DIVA software. Analysis was completed using FlowJo software. Statistics were performed using an unpaired t‐test with a p<.05 to indicate significance. Results Animals treated with a PO2 = 319 torr showed an increase (p = 0.045) in mobilized CD133+/34 endothelial progenitor cells (EPC's), while no differences were seen in CD133−/34+ hematopoietic stem progenitor cells (HSPC's) when compared to the control group. Discussion We hypothesized that there would be an increase in the CD133+/34− EPC's and an increase in CD133−/34+ HSPC's. Although our hypothesis was correct regarding the EPC's we did not see an increase in HSPC's as expected. CD133+/34− EPC's are considered more primitive stem cells than the CD133−/34+ HSPC's. CD133+/34− EPC's are capable of differentiation into CD133−/34+ HSPC's as they progress along the oligopotent path to maturation. Future research should include a pathological condition to test for changes in stem cell populations and the effects of pathology on stem cell differentiation. Our data suggest that low doses of daily intermittent hyperoxia mobilize the population of CD133+/34− EPC's. These EPC's have been shown in vivo to increase vascular density in a skin graft model. Further study is needed to determine what amount of intermittent hyperoxia treatment results in the most efficacious treatment in an injury model (increased stem cell mobilization, vasculogenesis and functional recovery). Support or Funding Information DOD Navy ‐ N00024‐17‐C‐4318 This abstract is from the Experimental Biology 2018 Meetin...

show abstract

“…This method worked concurrently to identify the salvageable tissue in penumbra based on the glucose metabolic status in MCAO rats. However, the disadvantages of OCI are, as mentioned above, the poor signal-to-noise due to the limited oxygen that delivered to the tissues and the artifacts caused by the paramagnetic effect of 100% O 2 within the paranasal sinuses (120).…”

Section: Oxygen Challenge Imagingmentioning

confidence: 99%

Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers

Mei

Hou

et al. 2021

Front. Neurol.

View full text Add to dashboard Cite

In acute stroke management, time window has been rigidly used as a guide for decades and the reperfusion treatment is only available in the first few limited hours. Recently, imaging-based selection of patients has successfully expanded the treatment window out to 16 and even 24 h in the DEFUSE 3 and DAWN trials, respectively. Recent guidelines recommend the use of imaging techniques to guide therapeutic decision-making and expanded eligibility in acute ischemic stroke. A tissue window is proposed to replace the time window and serve as the surrogate marker for potentially salvageable tissue. This article reviews the evolution of time window, addresses the advantage of a tissue window in precision medicine for ischemic stroke, and discusses both the established and emerging techniques of neuroimaging and their roles in defining a tissue window. We also emphasize the metabolic imaging and molecular imaging of brain pathophysiology, and highlight its potential in patient selection and treatment response prediction in ischemic stroke.

show abstract

Preclinical Validation of the Therapeutic Potential of Glasgow Oxygen Level Dependent (GOLD) Technology: a Theranostic for Acute Stroke

Cited by 14 publications

References 42 publications

Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model

Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model

Effect of intermittent hyperoxia on stem cell mobilization and cytokine expression

Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers

Contact Info

Product

Resources

About