Ischemic preconditioning and clinical scenarios.
ABSTRACT PURPOSE OF REVIEW: Ischemic preconditioning (IPC) is gaining attention as a novel neuroprotective therapy and could provide an improved mechanistic understanding of tolerance to cerebral ischemia. The purpose of this article is to review the recent work in the field of IPC and its applications to clinical scenarios. RECENT FINDINGS: The cellular signaling pathways that are activated following IPC are now better understood and have enabled investigators to identify several IPC mimetics. Most of these studies were performed in rodents, and efficacy of these mimetics remains to be evaluated in human patients. Additionally, remote ischemic preconditioning (RIPC) may have higher translational value than IPC. Repeated cycles of temporary ischemia in a remote organ can activate protective pathways in the target organ, including the heart and brain. Clinical trials are underway to test the efficacy of RIPC in protecting brain against subarachnoid hemorrhage. SUMMARY: IPC, RIPC, and IPC mimetics have the potential to be therapeutic in various clinical scenarios. Further understanding of IPC-induced neuroprotection pathways and utilization of clinically relevant animal models are necessary to increase the translational potential of IPC in the near future.
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ABSTRACT: Since the discovery of microRNAs, ample research has been conducted to elucidate their involvement in an array of (patho)physiological conditions. Ischemia reperfusion injury is a major problem in kidney transplantation and its mechanism is still not fully known, nor is there an effective therapy. Furthermore, no biomarker is available to specifically measure (ischemic) damage after kidney transplantation or predict transplantation outcome. In this review, we summarize studies conducted on microRNAs in renal ischemia reperfusion injury and kidney transplantation. Although the number of publications on miRNAs in different areas of nephrology is increasing every year, only a limited number of reports that address the role of miRNAs in relation to ischemia reperfusion injury or kidney transplantation are available. All reports up to June 2014 on microRNAs in renal IRI, kidney transplantation, and renal allograft status were included. Design of the studies was highly variable and there was limited overlap between microRNAs found in these reports. No single microRNA expression pattern could be found, although multiple microRNAs involved in the immune response seem to be altered after ischemia reperfusion injury and kidney transplantation. Although there is a growing interest in microRNA research in kidney transplantation aiming to identify biomarkers and therapeutical targets, to date, no specific microRNA has been demonstrated to be applicable as either one, mostly because of lack of specificity. More systematical research is needed to determine whether microRNAs can be applied as biomarker, therapeutic target, or therapeutic agent in kidney transplantation.Journal of Transplantation 05/2015; 2015. DOI:10.1155/2015/354826
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ABSTRACT: Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance.Dose-Response 12/2014; 12(4):619-49. DOI:10.2203/dose-response.14-032.Agrawal · 1.23 Impact Factor
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ABSTRACT: Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance). These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning) can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance (IT) in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral IT acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish IT and that IT can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of IT and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies.Frontiers in Neuroscience 03/2014; 8:44. DOI:10.3389/fnins.2014.00044