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Journal ArticleDOI

Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations.

01 Aug 2016-Pharmacological Research (Academic Press)-Vol. 110, pp 242-264
TL;DR: It is shown that pre- and postconditioning are specific types of hormesis, and the first documentation that hormetic effects account for preconditioning induced early and delayed windows of protection are provided.
About: This article is published in Pharmacological Research.The article was published on 2016-08-01. It has received 161 citations till now. The article focuses on the topics: Hormesis.
Citations
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Journal ArticleDOI
TL;DR: Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities that are over an order of magnitude above those produced by conventional tDCS.

874 citations

Journal ArticleDOI
15 Sep 2017
TL;DR: A working compartmentalization of hormesis is established into ten categories that provide an integrated understanding of the biological meaning and applications of horm Genesis to aid in designing and interpreting future studies.
Abstract: Hormesis refers to adaptive responses of biological systems to moderate environmental or self-imposed challenges through which the system improves its functionality and/or tolerance to more severe challenges. The past two decades have witnessed an expanding recognition of the concept of hormesis, elucidation of its evolutionary foundations, and underlying cellular and molecular mechanisms, and practical applications to improve quality of life. To better inform future basic and applied research, we organized and re-evaluated recent hormesis-related findings with the intent of incorporating new knowledge of biological mechanisms, and providing fundamental insights into the biological, biomedical and risk assessment implications of hormesis. As the literature on hormesis is expanding rapidly into new areas of basic and applied research, it is important to provide refined conceptualization of hormesis to aid in designing and interpreting future studies. Here, we establish a working compartmentalization of hormesis into ten categories that provide an integrated understanding of the biological meaning and applications of hormesis.

283 citations

Journal Article
01 Jul 2004-Stroke
TL;DR: Treatment with rhEPO significantly improved functional recovery, along with increases in density of cerebral microvessels at the stroke boundary and numbers of BrdU, doublecortin, and nestin immunoreactive cells in the SVZ.
Abstract: Background and Purpose— Erythropoietin (EPO) promotes proliferation and differentiation of erythroid progenitors and the survival of maturing erythroid cells. Here, we investigated the role of EPO in brain repair after stroke. Methods— Rats were treated with recombinant human EPO (rhEPO) at 24 hours after the onset of embolic stroke. An array of behavior tests was performed. Rats were euthanized 28 days after stroke for measurements of infarct volume, angiogenesis, and neurogenesis. In vitro, neurospheres derived from the subventricular zone (SVZ) of the rat and cerebral endothelial cells derived from the mouse were treated with rhEPO. Capillary-like tube formation and neuronal differentiation were measured. Results— Treatment with rhEPO significantly improved functional recovery, along with increases in density of cerebral microvessels at the stroke boundary and numbers of BrdU, doublecortin, and nestin immunoreactive cells in the SVZ. rhEPO treatment significantly increased brain levels of vascular endo...

170 citations

Journal ArticleDOI
TL;DR: The present analysis reveals that hormetic biphasic dose responses were associated with both the conditioning process and the protective effects elicited following the challenging dose, indicating that the biological/biomedical effects induced by conditioning represent a specific type of hormetic dose response and thereby contribute significantly to a generalization of the hormetic concept.

157 citations

Journal ArticleDOI
TL;DR: The most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research were discussed at a recent meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine as mentioned in this paper.
Abstract: The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose-response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged.

146 citations

References
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Journal ArticleDOI
TL;DR: The multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy, which is proposed to protect the heart from a subsequent sustained ischemic insult.
Abstract: We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes. Additionally, intermittent reperfusion may be beneficial to the myocardium by washing out catabolites that have accumulated during ischemia. Thus, we proposed that multiple brief ischemic episodes might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set, one group of dogs (n = 7) was preconditioned with four 5 min circumflex occlusions, each separated by 5 min of reperfusion, followed by a sustained 40 min occlusion. The control group (n = 5) received a single 40 min occlusion. In the second study, an identical preconditioning protocol was followed, and animals (n = 9) then received a sustained 3 hr occlusion. Control animals (n = 7) received a single 3 hr occlusion. Animals were allowed 4 days of reperfusion thereafter. Histologic infarct size then was measured and was related to the major baseline predictors of infarct size, including the anatomic area at risk and collateral blood flow. In the 40 min study, preconditioning with ischemia paradoxically limited infarct size to 25% of that seen in the control group (p less than .001). Collateral blood flows were not significantly different in the two groups. In the 3 hr study, there was no difference between infarct size in the preconditioned and control groups. The protective effect of preconditioning in the 40 min study may have been due to reduced ATP depletion and/or to reduced catabolite accumulation during the sustained occlusion. These results suggest that the multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy.

7,750 citations

Journal ArticleDOI
TL;DR: Data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries, and the neurotrophic actions suggest there may be longer-latency effects as well.
Abstract: Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1–10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.

1,045 citations


Additional excerpts

  • ...…and NonMechanism Studies References 41 Erythropoietin (EPO) X X X Chong et al., 2002, 2003, 2011 [115- 117]; Jones et al., 2013 [99]; Ma et al., 2009 [118]; Ma et al., 2013 [119]; Shi et al., 2004 [120]; Siren et al., 2001 [121]; Wang et al., 2004 [122]; Yu et al., 2005 [123] 42 Estradiol (17-...

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Journal ArticleDOI
TL;DR: It is demonstrated that the delivery of H2S at the time of reperfusion limits infarct size and preserves left ventricular (LV) function in an in vivo model of myocardial ischemia-reperfusion (MI-R) and that either administration of H 2S or the modulation of endogenous production may be of clinical benefit in ischemic disorders.
Abstract: The recent discovery that hydrogen sulfide (H2S) is an endogenously produced gaseous second messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential of H2S as a cardioprotective agent. In the current study, we demonstrate that the delivery of H2S at the time of reperfusion limits infarct size and preserves left ventricular (LV) function in an in vivo model of myocardial ischemia-reperfusion (MI-R). This observed cytoprotection is associated with an inhibition of myocardial inflammation and a preservation of both mitochondrial structure and function after I-R injury. Additionally, we show that modulation of endogenously produced H2S by cardiac-specific overexpression of cystathionine γ-lyase (α-MHC-CGL-Tg mouse) significantly limits the extent of injury. These findings demonstrate that H2S may be of value in cytoprotection during the evolution of myocardial infarction and that either administration of H2S or the modulation of endogenous production may be of clinical benefit in ischemic disorders.

1,012 citations


Additional excerpts

  • ...…Hydrogen sulfide (H2S) X X X Bian et al., 2006 [159]; Chen et al., 2013 [160]; Cheng et al., 2014 [161]; Dongo et al., 2014 [162]; Elrod et al., 2007 [163]; Hu et al., 2008 [164]; Jha et al., 2008 [55]; Ji et al., 2008 [165]; Johansen et al., 2006 [166]; Li et al., 2013 [167]; Li…...

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Journal ArticleDOI
10 Feb 1984-Science
TL;DR: When human lymphocytes were cultured with [3H]thymidine, which acts as a source of low-level chronic radiation, and then exposed to 150 rad of x-rays at 5, 7, 9, or 11 hours before fixation, the yield of chromatid aberrations was less than the sum of the yields of aberration induced by [3 H]thcyidine and x-ray separately.
Abstract: When human lymphocytes were cultured with [3H]thymidine, which acts as a source of low-level chronic radiation, and then exposed to 150 rad of x-rays at 5, 7, 9, or 11 hours before fixation, the yield of chromatid aberrations was less than the sum of the yields of aberrations induced by [3H]thymidine and x-rays separately. Often fewer aberrations were found after exposure to radiation from both sources than were found after exposure to x-rays alone. At the same fixation times, nonradioactive thymidine did not affect the yield of x-ray-induced aberrations. The same phenomenon occurred at earlier fixation times, after exposure to 30 or 40 rad of x-rays and [3H]thymidine. This response is analogous to the adaptive response to alkylating agents whereby prior treatment with small doses for a long period reduces the damage occurring from large doses of similar agents given for a short time.

804 citations

Journal ArticleDOI
01 Jul 2004-Stroke
TL;DR: The data suggest that EPO-increased VEGF and BDNF may be involved in angiogenesis and neurogenesis, which could contribute to functional recovery.
Abstract: Background and Purpose— Erythropoietin (EPO) promotes proliferation and differentiation of erythroid progenitors and the survival of maturing erythroid cells. Here, we investigated the role of EPO in brain repair after stroke. Methods— Rats were treated with recombinant human EPO (rhEPO) at 24 hours after the onset of embolic stroke. An array of behavior tests was performed. Rats were euthanized 28 days after stroke for measurements of infarct volume, angiogenesis, and neurogenesis. In vitro, neurospheres derived from the subventricular zone (SVZ) of the rat and cerebral endothelial cells derived from the mouse were treated with rhEPO. Capillary-like tube formation and neuronal differentiation were measured. Results— Treatment with rhEPO significantly improved functional recovery, along with increases in density of cerebral microvessels at the stroke boundary and numbers of BrdU, doublecortin, and nestin immunoreactive cells in the SVZ. rhEPO treatment significantly increased brain levels of vascular endo...

727 citations

Related Papers (5)
Trending Questions (1)
Does preconditioning in hormesis provide permanent protection?

The paper does not provide information on whether preconditioning in hormesis provides permanent protection.