Role of hypoxia inducible factor-1α in remote limb ischemic preconditioning

Kalakech, Hussein; Tamareille, Sophie; Pons, Sandrine; Godin‐Ribuot, Diane; Carmeliet, Peter; Furber, Alain; Martin, Valérie; Berdeaux, A; Ghaleh, Bijan; Prunier, Fabrice

doi:10.1016/j.yjmcc.2013.10.001

“…In a time course study of responses to peripheral LPS challenge, Norden et al [20] found that microglia are activated first, followed by astrocytes. Furthermore, microglial IL-10 stimulates astrocytic TGF-β in response to LPS challenge [27]. The large overlap between molecular pathways activated in response to LPS and ischemia is, in part, responsible for the phenomenon of crosstolerance (discussed previously), suggesting that IPC may modulate microglia/astrocyte interplay, with both cells playing important roles in conferring IPC-mediated neuroprotection.…”

Section: Astrocytesmentioning

confidence: 87%

“…Mxultiple CNS cells [18,26] histone modulators TNF-α Neuroprotectant and/or proapoptotic Astrocytes [19][20][21], microglia [19][20][21], peripheral immune cells [19][20][21] Neuroprotective IRFs Downstream mediators of the reprogrammed genomic response to ischemia Microglia [11], macrophages [11] TLRs Reprograms cellular genomic response to ischemia Circulating leukocytes [16], endothelial cells [16], microglia [17,18] TGF-β Promotes repair of neurovascular unit, regulates immune system function Astrocytes [20,27], microglia [27], T cells [28] TLR = Toll-like receptor; TNF = tumor necrosis factor; NFkB = nuclear factor kB; CNS = central nervous system; HIF = hypoxia-inducible factor; IFN = interferon; IRF = IFN regulatory factor; TGF = transforming growth factor geared at less invasive methods of inducing preconditioning. These include the administration of therapeutics, such as cytokines or TLR agonists which play a role in preconditioning, or the concept of remote IPC (RIPC), which uses remote limb ischemia to induce neuroprotection equivalent to direct preconditioning of the brain using models of focal ischemia [4,30,31].…”

Section: Hif-1mentioning

confidence: 99%

“…Astrocytes also produce many regulatory factors that may provide negative feedback to microglia, helping to modulate microglial activation states. In one example, TGF-β produced by astrocytes, in response to IL-10 secretion by microglia, provides negative feedback on microglial activation [27]. In another study, knockdown of astrocytic GAP43 led to increased microglial activation in the context of LPS challenge [109], suggesting that GAP43 expression in astrocytes attenuates the LPS-based immune response in microglia.…”

Section: Astrocytesmentioning

confidence: 99%

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Neuroimmune Response in Ischemic Preconditioning

McDonough

¹

,

Weinstein

²

2016

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Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Toll-like receptors and type 1 interferons. Brain ischemia results in release of proand anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammtory response, resolution of inflammation, and transition to neurological recovery and regeneration. Cellular mediators of IPC include microglia, the resident central nervous system immune cells, astrocytes, and neurons. All of these cell types engage in cross-talk with each other using a multitude of signaling pathways that modulate activation/ suppression of each of the other cell types in response to ischemia. As the postischemic neuroimmune response evolves over time there is a shift in function toward provision of trophic support and neuroprotection. Peripheral immune cells infiltrate the central nervous system en masse after stroke and are largely detrimental, with a few subtypes having beneficial, protective effects, though the role of these immune cells in IPC is largely unknown. The role of neural progenitor cells in IPC-mediated neuroprotection is another active area of investigation as is the role of microglial proliferation in this setting. A mechanistic understanding of these molecular and cellular mediators of IPC may not only facilitate more effective direct application of IPC to specific clinical scenarios, but also, more broadly, reveal novel targets for therapeutic intervention in stroke.

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“…263 The role of HIF1α in RIPC is controversial because one study showed skeletal muscle HIF1α important for interleukin 10 formation and IS reduction by limb RIC after 24 hours, 264 whereas in another study, using the same heterozygous HIF1α-deficient mice limb RIC still reduced IS, however, without a 24 hours time lag. 265 …”

mentioning

confidence: 99%

Molecular Basis of Cardioprotection

Heusch

¹

2015

Circulation Research

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Abstract:Reperfusion is mandatory to salvage ischemic myocardium from infarction, but reperfusion per se contributes to injury and ultimate infarct size. Therefore, cardioprotection beyond that by timely reperfusion is needed to reduce infarct size and improve the prognosis of patients with acute myocardial infarction. The conditioning phenomena provide such cardioprotection, insofar as brief episodes of coronary occlusion/ reperfusion preceding (ischemic preconditioning) or following (ischemic postconditioning) sustained myocardial ischemia with reperfusion reduce infarct size. Even ischemia/reperfusion in organs remote from the heart provides cardioprotection (remote ischemic conditioning). The present review characterizes the signal transduction underlying the conditioning phenomena, including their physical and chemical triggers, intracellular signal transduction, and effector mechanisms, notably in the mitochondria. Cardioprotective signal transduction appears as a highly concerted spatiotemporal program. Although the translation of ischemic postconditioning and remote ischemic conditioning protocols to patients with acute myocardial infarction has been fairly successful, the pharmacological recruitment of cardioprotective signaling has been largely disappointing to date.

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“…The pioneering papers in the RIPC field suggest that neuroprotection is induced rapidly [30,31,37]; however, the duration of protection has not been determined [37,38]. Molecular determinants behind the phenomenon of RIPC have not been fully elucidated, but there is some evidence of overlap with molecular mediators of ischemic and LPS preconditioning, including hypoxia-inducible factor (HIF)-1α [39], and inflammatory factors [40][41][42][43]. Remote limb ischemia may induce global expression of these molecular mediators of preconditioning that confers protection to multiple organ systems, including the brain.…”

Section: Remote Preconditioningmentioning

confidence: 99%

Correction to: Neuroimmune Response in Ischemic Preconditioning

McDonough

¹

,

Weinstein

²

2018

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Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Tolllike receptors and type 1 interferons. Brain ischemia results in release of pro-and anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammatory response, resolution of inflammation, and transition to neurological recovery and regeneration. Cellular mediators of IPC include microglia, the resident central nervous system immune cells, astrocytes, and neurons. All of these cell types engage in cross-talk with each other using a multitude of signaling pathways that modulate activation/ suppression of each of the other cell types in response to ischemia. As the postischemic neuroimmune response evolves over time there is a shift in function toward provision of trophic support and neuroprotection. Peripheral immune cells infiltrate the central nervous system en masse after stroke and are largely detrimental, with a few subtypes having beneficial, protective effects, though the role of these immune cells in IPC is largely unknown. The role of neural progenitor cells in IPC-mediated neuroprotection is another active area of investigation as is the role of microglial proliferation in this setting. A mechanistic understanding of these molecular and cellular mediators of IPC may not only facilitate more effective direct application of IPC to specific clinical scenarios, but also, more broadly, reveal novel targets for therapeutic intervention in stroke. Keywords PreconditioningIschemic preconditioning (IPC) is an experimental phenomenon in which a brief period of ischemia confers robust neuroprotection against subsequent ischemic events [1-3]. It is important to note that preconditioning does not reduce the incidence of stroke, but rather ameliorates the pathophysiologic response to cerebral ischemia and results in a smaller infarct volume and improved poststroke recovery [4][5][6]. Clinical studies suggest that patients with stroke who suffered a recent prior transient ischemic attack have better outcomes than those who did not, implying that a human correlate to experimental IPC exists [7,8]. Elucidating the mechanisms of IPC is considered a critical challenge in stroke research [9,10]. Recent literature has implicated innate immune pathways, including Toll-like receptors (TLRs) [11,12] and type 1 interferon (IFN) signaling [5,11,13] in IPC-mediated protection.Due to a technical error in the production process, the earlier version of this article contained numerous errors in the reference numbering. We are reprinting the entire article in the correction for readabilityThe online version of the original article can be found at https://doi

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Role of hypoxia inducible factor-1α in remote limb ischemic preconditioning

Cited by 57 publications

References 53 publications

Neuroimmune Response in Ischemic Preconditioning

Neuroimmune Response in Ischemic Preconditioning

Molecular Basis of Cardioprotection

Correction to: Neuroimmune Response in Ischemic Preconditioning

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