Trace Amounts of Copper in Drinking Water Aggravate Cerebral Ischemic Injury via Impairing Endothelial Progenitor Cells in Mice

Background/Aims: Chronic cold exposure may increase energy expenditure and contribute to counteracting obesity, an important risk factor for cerebrocardiovascular diseases. This study sought to evaluate whether preventive cold acclimation before ischemia onset might be a promising option for preventing cerebral ischemic injury. Methods: After a 14-day cold acclimation period, young and aged mice were subjected to permanent cerebral ischemia, and histological analyses and behavioral tests were performed. Mouse endothelial progenitor cells (EPCs) were isolated, their function and number were determined, and the effects of EPC transplantation on cerebral ischemic injury were investigated. Results: Preventive cold acclimation before ischemia onset increased EPC function, promoted ischemic brain angiogenesis, protected against cerebral ischemic injury, and improved long-term stroke outcomes in young mice. In addition, transplanted EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic injury and promote local angiogenesis compared to those from control mice, and EPCs from donor animals could integrate into the recipient ischemic murine brain. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury, which could be improved by preventive cold acclimation. Moreover, preventive cold acclimation could also enhance EPC function, promote local angiogenesis, and protect against cerebral ischemic injury in aged mice. Conclusions: Preventive cold acclimation before ischemia onset improved long-term stroke outcomes in mice at least in part via promoting the reparative function of EPC. Our findings imply that a variable indoor environment with frequent cold exposure might benefit individuals at high risk for stroke.

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A preventive injection of endothelial progenitor cells prolongs lifespan in stroke-prone spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs20180360 ◽

2018 ◽

Vol 132 (16) ◽

pp. 1797-1810 ◽

Cited By ~ 2

Author(s):

Cheng Peng ◽

Xiao-Hui Dong ◽

Jia-Lin Liu ◽

Yu-Long Tao ◽

Chun-Fang Xu ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Spontaneously Hypertensive Rats ◽

Single Injection ◽

Ischemic Injury ◽

Hypertensive Rats ◽

Ischemic Brain ◽

Spontaneously Hypertensive ◽

Cerebral Ischemic Injury ◽

Cerebral Ischemic

There is a pressing need for new approaches to prevent stroke. Endothelial progenitor cells (EPCs) promote vascular repair and revascularization in the ischemic brain. The present study sought to evaluate whether preventive delivery of EPCs could prevent or protect against stroke. Stroke-prone spontaneously hypertensive rats (SHR-SP) received a single injection of EPCs, and their survival time was monitored. In addition, at 28 and/or 42 days after a single injection of EPCs, SHR-SP and mice were subjected to cerebral ischemia, and cerebral ischemic injury, local angiogenesis and in vivo EPC integration were determined. Other experiments examined the effects of EPC conditioned medium, and the distribution of donor EPCs taken from GFP transgenic mice. It was found that EPC-pretreated SHR-SP showed longer lifespans than untreated controls. A single preventive injection of EPCs could produce persistent protective effects against cerebral ischemic injury (lasting at least 42 days), and promote local angiogenesis in the ischemic brain, in two types of animals (SHR-SP and normotensive mice). EPCs of donor origin could be detected in the recipient peripheral blood, and integrated into the recipient ischemic brains. Furthermore, it was suggested that mouse EPCs might exert paracrine effects on cerebral ischemic injury in addition to their direct angiogenic effects. In conclusion, a single preventive injection of EPCs prolonged the lifespan of SHR-SP, and protected against cerebral ischemic injury for at least 7 weeks. It is implied that EPC injection might be a promising candidate for a preventive role in patients at high risk for stroke.

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Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2021.689880 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiao-Hui Dong ◽

Cheng Peng ◽

Yu-Yi Zhang ◽

Yu Jiang ◽

Li-Jun Yang ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

High Fat Diet ◽

Low Dose ◽

Ischemic Injury ◽

High Fat ◽

Angiogenic Potential ◽

Ischemic Diseases ◽

Cerebral Ischemic Injury ◽

Cerebral Ischemic

It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs’ angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O2- level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 μM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs’ angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases.

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Prolonged Fasting Improves Endothelial Progenitor Cell-Mediated Ischemic Angiogenesis in Mice

Cellular Physiology and Biochemistry ◽

10.1159/000452581 ◽

2016 ◽

Vol 40 (3-4) ◽

pp. 693-706 ◽

Cited By ~ 6

Author(s):

Bao Xin ◽

Chun-Long Liu ◽

Hong Yang ◽

Cheng Peng ◽

Xiao-Hui Dong ◽

...

Keyword(s):

Cerebral Ischemia ◽

Endothelial Progenitor Cell ◽

Progenitor Cell ◽

Ischemic Injury ◽

Prolonged Fasting ◽

Endothelial Progenitor ◽

Ischemic Brain ◽

Cerebral Ischemic Injury ◽

Cerebral Ischemic

Background/Aims: Prolonged fasting (PF) was shown to be of great potency to promote optimal health and reduce the risk of many chronic diseases. This study sought to determine the effect of PF on the endothelial progenitor cell (EPC)-mediated angiogenesis in the ischemic brain and cerebral ischemic injury in mice. Methods: Mice were subjected to PF or periodic PF after cerebral ischemia, and histological analysis and behavioral tests were performed. Mouse EPCs were isolated and examined, and the effects of EPC transplantation on cerebral ischemic injury were investigated in mice. Results: It was found that PF significantly increased the EPC functions and angiogenesis in the ischemic brain, and attenuated the cerebral ischemic injury in mice that was previously subjected to cerebral ischemia. Periodic PF might reduce cortical atrophy and improve long-term neurobehavioral outcomes after cerebral ischemia in mice. The eNOS and MnSOD expression and intracellular NO level were increased, and TSP-2 expression and intracellular O2- level were reduced in EPCs from PF-treated mice compared to control. In addition, transplanted EPCs might home into ischemic brain, and the EPCs from PF-treated mice had a stronger ability to promote angiogenesis in ischemic brain and reduce cerebral ischemic injury compared to the EPCs from control mice. The EPC-conditioned media from PF-treated mice exerted a stronger effect on cerebral ischemic injury reduction compared to that from control mice. Conclusion: Prolonged fasting promoted EPC-mediated ischemic angiogenesis and improved long-term stroke outcomes in mice. It is implied that prolonged fasting might potentially be an option to treat ischemic vascular diseases.

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