Conditioning medicine最新文献

{"title":"Targeting leukotriene biosynthesis to prevent atherosclerotic cardiovascular disease.","authors":"Xiaomeng Wang, Lohendran Baskaran, Mark Chan, William Boisvert, Derek J Hausenloy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide. As such, new treatments are needed to prevent the onset and progression of atherosclerosis to improve outcomes in patients with coronary, cerebrovascular, and peripheral arterial disease. In this regard, inflammation is known to be a critical driver of atherosclerosis formation and progression, thus it is a viable target for vascular protection in patients at risk of developing ASCVD. Leukotrienes, key pro-inflammatory lipid mediators derived from arachidonic acid, are associated with atheroma inflammation and progression. Genetic mutations in key components of the leukotriene synthesis pathway, such as 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP), are associated with an increased risk of cardiovascular disease, and pharmacological inhibition of 5-LO and FLAP has been reported to prevent atheroma formation in pre-clinical and early clinical studies. In this article, we provide an overview of these studies and highlight the therapeutic potential of targeting leukotriene synthesis to prevent atheroma inflammation and progression and improve outcomes in patients at risk of ASCVD.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"6 2","pages":"33-41"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11126214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: Can astrocytic mitochondria therapy be used as antioxidant conditioning to protect neurons?","authors":"Kazuhide Hayakawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the context of central nervous system (CNS) disease, oxidative stress may cause progression of cell death and neuroinflammation. Therefore, restoring mitochondrial antioxidant ability within cells is a major therapeutic strategy in many CNS disorders. A recent study uncovers a novel mechanism of astrocytic mitochondria being neuroprotective after intracerebral hemorrhage in mice. In their work, systemic administration of mitochondria obtained from astrocytes restores neuronal antioxidant defense, prevents neuronal death while promoting neurite outgrowth, indicating that extracellular mitochondria may play key roles in mediating beneficial non-cell autonomous effects. Given that mitochondria are also responsible for tolerance to stress and injury, is it possible that exogenous mitochondria signals may regulate cellular conditioning by boosting antioxidant ability? Further studies are warranted to build on these emerging findings in the pursuit of conditioning therapies mediated by mitochondrial transplantation in CNS injury and disease.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"5 6","pages":"192-195"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of circadian rhythm in ischemic stroke outcomes.","authors":"P. Kamat, Mohammad B. Khan, Kristofer Wood, Shahneela Siddiqui, D. Rudic, K. Dhandapani, Jennifer Waller, D. Hess","doi":"10.1161/str.53.suppl_1.wmp118","DOIUrl":"https://doi.org/10.1161/str.53.suppl_1.wmp118","url":null,"abstract":"Stroke is a leading cause of disability and death worldwide. There is evidence that there is a circadian rhythm in stroke with peak occurrence in the morning (6 to 10 am). However, it is not clear if the size of infarcts and the outcome of stroke also varies during the 24-hour period. We hypothesized that the size of cerebral infarct and outcome from stroke would show circadian variation in a mouse suture occlusion model. Seven to eight-month-old C57BL/6J (n =10-12 mice/group) mice were randomly assigned to undergo middle cerebral artery occlusion (MCAO) for 60 minutes at different time points during the 24h day following zeitgeber time at ZT0, ZT6, ZT12, and Z18. Cerebral blood flow was monitored by Laser Speckle Contrast Imaging at baseline after occlusion, and again at 24h post-occlusion. Neurological deficit was observed by using Bederson score at 24h and 48h. The corner test was used to detect unilateral abnormalities in sensory and motor functions in the stroke mice at 48h. To estimate brain infarction, 2,3,5-tryphenyltetrazolium chloride staining was performed 48h after stroke and the infarct area was quantified using NIH-Image J software. We did not find a significant difference in cerebral blood flow at any time point. There was a significant decrease in neurological deficit as assessed using the Bederson Score from 24h (1.82 ± 1.11) to 48h (1.10 ± 0.12) in the ZT18 (midnight) period (p = 0.0025), however there were no differences between groups at 48h. In the corner test, we found right turn preference significantly higher (p = 0.0348) at noon/ZT06 (9.5 ± 1.06) compared to the fully awake (5.5 ± 4.06) (midnight, ZT18) period and ZT0 (6 am, 4.8 ± 0.97, p = 0.0087). Similarly, the infarction volume was significantly higher (p = 0.0220) during the sleep (ZT06, noon) period (35.22 ± 20.77) than when the ischemic mice were fully awake during the midnight/ZT18 period (15.68 ± 7.54). This is the first report demonstrating that mice have larger infarcts and worse short-term outcomes during their sleep period (noon/ZT06) than during their awake period (midnight/ZT18).","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"4 6 1","pages":"280-284"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45231271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conditioning medicine for ischemic and hemorrhagic stroke.","authors":"David C Hess,&nbsp;Mohammad Badruzzaman Khan,&nbsp;Pradip Kamat,&nbsp;Kumar Vaibhav,&nbsp;Krishnan M Dhandapani,&nbsp;Babak Baban,&nbsp;Jennifer L Waller,&nbsp;Md Nasrul Hoda,&nbsp;Rolf Ankerlund Blauenfeldt,&nbsp;Grethe Andersen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Remote ischemic conditioning (RIC) is a promising safe, feasible, and inexpensive treatment for acute stroke, both ischemic and hemorrhagic. It is applied with a blood pressure cuff on the limbs and is ideal for the prehospital setting. RIC is a form of preconditioning with similarities to physical exercise. Its mechanisms of action are multiple and include improvement of collateral cerebral blood flow (CBF) and RIC acts as a \"collateral therapeutic\". The increased CBF is likely related to nitric oxide synthase 3 in the endothelium and more importantly in circulating blood cells like the red blood cell. The RESIST clinical trial is a 1500 subject multicenter, randomized, sham-controlled trial of RIC in the prehospital setting in Denmark and should address the questions of whether RIC is safe and effective in acute stroke and whether the effect is mediated by an effect on nitric oxide/nitrite metabolism.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"4 3","pages":"124-129"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372992/pdf/nihms-1725141.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9622405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria as the memory of preconditioning.","authors":"Sarah Zerimech, Hung Nguyen, Selva Baltan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Preconditioning is such a paradigm that a stimulus below the threshold of causing harm makes the brain stronger and resilient to subsequent injury. Preconditioning affords a vigorous tolerance to the brain against neurodegeneration. Numerous efforts have tried to identify the molecular targets involved in preconditioning-induced protective responses and interestingly many of those diverse mechanisms posit mitochondria as a master regulator of preconditioning. Therefore, in this review, we will critically discuss recent and emerging evidence for the involvement of mitochondria within the preconditioning paradigm. We will introduce the crucial targets and signaling cascades by which mitochondria exert preconditioning with a focus on white matter mitochondria and whether and how mechanisms for preconditioning differ in neurons and glial cells. In this aspect, we will evaluate the role of mitochondrial shaping proteins to establish structure-function interdependence for fusion-fission balance, motility, ATP production, Ca⁺², and ROS scavenging. We will also discuss how aging impacts mitochondria and the consequences of mitochondrial aging on preconditioning mechanisms. We will concentrate on the regulation of mitochondrial DNA content and quantification specifically for its value as a biomarker to monitor disease conditions. The identification of these mitochondrial preconditioning mechanisms can be translated to potential pharmacological interventions to increase intrinsic resilience of the brain to injury and to develop novel approaches to neurodegenerative diseases. Moreover, mitochondria dynamics can be used as a memory or biomarker of preconditioning.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":" ","pages":"151-160"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484407/pdf/nihms-1787747.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40373758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the immune system for conditioning in cerebrovascular diseases.","authors":"Ann M Stowe,&nbsp;Jürgen Bernhagen","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":" ","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177088/pdf/nihms-1707730.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39069814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential regulation of cerebral microvascular transcription by single and repetitive hypoxic conditioning.","authors":"Jarrod C Harman,&nbsp;David A Otohinoyi,&nbsp;John W Reitnauer,&nbsp;Ann M Stowe,&nbsp;Jeff M Gidday","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Systemic conditioning therapeutics afford brain protection at all levels of organization, occurring autonomously for neurons, glia, vascular smooth muscle, and endothelium, which are mediated systemically for the adaptive and innate immune system. The present study was undertaken to examine acute (3 h) and delayed (2 days) gene expression changes in mouse cerebral microvessels following single hypoxic conditioning (HX1) and repetitive hypoxic conditioning (HX9), the latter for which we showed previously to extend focal stroke tolerance from days to months. Microarray (Illumina) analyses were performed on microvessel-enriched fractions of adult mouse brain obtained from the following five groups (naïve; HX1-3h; HX1-2days; HX9-3h; HX9-2days). Differentially expressed genes were analyzed bioinformatically using Ingenuity Pathway Analysis software, with qPCR validating selected up- and down-regulated genes. As expected, some differentially expressed genes were common to more than one treatment or time point, whereas others were unique to treatment or time point. Bioinformatic analyses provided insights into acute (3h) inflammatory and immune signaling pathways that may be differentially activated by HX1 and HX9, with anti-inflammatory and trophic pathways coincident with the ischemia-tolerant phenotype two days after HX1. Interestingly, two days after HX9, microvessels were transcriptionally silent, with only five genes remaining differentially expressed relative to naïve mice. Our microarray findings and bioinformatic analyses suggest that cerebral microvessels from HX1-treated mice exhibit early activation of immune system signaling that is largely suppressed in microvessels from HX9-treated mice. These and other differences between these responses require further study, including at the proteomic level, and with pharmacologic and genetic experiments designed to reveal causality, to reveal further insights into the mechanisms underlying long-lasting stroke tolerance.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"4 1","pages":"58-68"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372757/pdf/nihms-1707729.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9529941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laboratory and clinical research on COVID-19: focus on non-lung organs.","authors":"Cesar V Borlongan,&nbsp;David C Hess","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 5","pages":"239-240"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205431/pdf/nihms-1648558.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39239442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 and neurological symptoms: is the SARS-CoV-2 virus neurotropic?","authors":"David C Hess,&nbsp;Elizabeth Rutkowski,&nbsp;John Morgan,&nbsp;Lynnette McCluskey","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Importance: </strong>The most notable symptoms of the Coronavirus Disease 2019 (COVID-19) pandemic are fever, cough, dyspnea, and in severe cases, adult respiratory distress syndrome (ARDS.) But neurological symptoms including confusion, stroke, and encephalopathy are reported, and anosmia and hypogeusia are also common indicating that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be neurotropic.</p><p><strong>Observations: </strong>The SARS-Co-1 and 2 viruses bind to angiotensin converting enzyme 2 (ACE2), which is present on human brain endothelium and non-neuronal cells in the nasopharynx and lingual epithelium. However, SARS-CoV-1 and 2 do not bind rodent ACE2 avidly, which has required the generation of humanized ACE2 transgenic animal models of disease. Transgenic mouse models suggest that the SARS- CoV-1 and Middle East respiratory syndrome (MERS)-CoV are neurotropic and infect and damage the brain, including the cardiorespiratory centers in the medulla. The symptoms of anosmia and hypogeusia indicate a portal to the brain. The relationship between encephalitis lethargica and post encephalitis parkinsonism to the Spanish Flu (H1N1 influenza virus) is unclear but raises the question of long term neurological complications of pandemics.</p><p><strong>Conclusions and relevance: </strong>There is a concern that there may be long term neurological sequelae of infection with SARS-CoV-2. Registries and long term neurological follow up with longitudinal cohort studies of COVID19 positive patients are needed.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 5","pages":"241-245"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205429/pdf/nihms-1648557.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39239443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles - mediating and delivering cardioprotection in acute myocardial infarction and heart failure.","authors":"Aishwarya Prakash,&nbsp;Gustavo E Crespo-Avilan,&nbsp;Sauri Hernandez-Resendiz,&nbsp;Sang-Ging Ong,&nbsp;Derek J Hausenloy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>New treatments are urgently needed to reduce myocardial infarct size and prevent adverse post-infarct left ventricular remodeling, in order to preserve cardiac function, and prevent the onset of heart failure in patients presenting with acute myocardial infarction (AMI). In this regard, extracellular vesicles (EVs) have emerged as key mediators of cardioprotection. Endogenously produced EVs are known to play crucial roles in maintaining normal cardiac homeostasis and function, by acting as mediators of intercellular communication between different types of cardiac cells. Endogenous EVs have also been shown to contribute to innate cardioprotective strategies such as remote ischemic conditioning. In terms of EV-based therapeutics, stem cell-derived EVs have been shown to confer cardioprotection in a large number of small and large animal AMI models, and have the therapeutic potential to be applied in the clinical setting for the benefit of AMI patients, although several challenges need to be overcome. Finally, EVs may be used as vehicles to deliver therapeutics to the infarcted heart, providing a potential synergist approach to cardioprotection. In this review article, we highlight the various roles that EVs play as mediators and deliverers of cardioprotection, and discuss their therapeutic potential for improving clinical outcomes following AMI.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 4","pages":"227-238"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294590/pdf/nihms-1631829.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39212296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}