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New Molecular Insights into Ischemia/Reperfusion

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 September 2024 | Viewed by 3420

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Special Issue Editor

Prof. Dr. Moo-Ho Won

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Guest Editor

Department of Emergency Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon 24289, Republic of Korea
Interests: ischemia/reperfusion; neurodegeneration; neurogenesis; cerebral ischemia; aging in CNS
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ischemia/reperfusion (IR) causes a complex pathophysiological process, called IR injury, defined as the paradoxical exacerbation of cellular dysfunction and death following the restoration of blood flow to previously ischemic tissues. IR injury happens in a wide range of organs including the heart, brain, spinal cord, gut, kidney, and skeletal muscle. IR injury not only involves the ischemic organ itself but also induces systemic damage to distant organs. Huge efforts have been made to develop potential treatments for IR injury, but the molecular and cellular mechanisms of IR injury are not fully understood regarding organs. Therefore, many researchers have been investigating the mechanisms of IR injury in diverse organs using various experimental animal models of IR injury (i.e., different methods of the occlusion of blood vessels and different periods of occlusion time). Principally, the mechanisms of IR injury include excitotoxicity, oxidative stress, and inflammation. Nevertheless, the mechanisms are significantly different according to organs. For instance, blood–brain (spinal cord) barrier damage is one of the mechanisms of IR injury in the central nervous system. Therefore, investigation into the molecular mechanisms of IR injury in various organs is warranted so that we can treat or protect against IR injury in the organs. Thus, this Special Issue will focus on “New Molecular Insights into Ischemia/Reperfusion” in various organs including the heart, brain, spinal cord, liver, and kidneys.

Prof. Dr. Moo-Ho Won
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

vital organs
ischemic injury
cell and organ dysfunction
oxidative stress
inflammation
excitotoxicity

Published Papers (4 papers)

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Research

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13 pages, 2229 KiB

Open AccessArticle

Neuroprotective Effects of Aucubin against Cerebral Ischemia and Ischemia Injury through the Inhibition of the TLR4/NF-κB Inflammatory Signaling Pathway in Gerbils

by Joon Ha Park, Tae-Kyeong Lee, Dae Won Kim, Ji Hyeon Ahn, Myoung Cheol Shin, Jun Hwi Cho, Moo-Ho Won and Il Jun Kang

Int. J. Mol. Sci. 2024, 25(6), 3461; https://doi.org/10.3390/ijms25063461 - 19 Mar 2024

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Abstract

Aucubin, an iridoid glycoside, possesses beneficial bioactivities in many diseases, but little is known about its neuroprotective effects and mechanisms in brain ischemia and reperfusion (IR) injury. This study evaluated whether aucubin exhibited neuroprotective effects against IR injury in the hippocampal CA1 region through anti-inflammatory activity in gerbils. Aucubin (10 mg/kg) was administered intraperitoneally once a day for one week prior to IR. Neuroprotective effects of aucubin were assessed by neuronal nuclei (NeuN) immunofluorescence and Floro-Jade C (FJC) histofluorescence. Microgliosis and astrogliosis were evaluated using immunohistochemistry with anti-ionized calcium binding adapter protein 1 (Iba1) and glial fibrillary acidic protein (GFAP). Protein levels of proinflammatory cytokines interleukin1 beta (IL1β) and tumor necrosis factor alpha (TNFα) were assayed using enzyme-linked immunosorbent assay and Western blot. Changes in toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway were assessed by measuring levels of TLR4, inhibitor of NF-κB alpha (IκBα), and NF-κB p65 using Western blot. Aucubin treatment protected pyramidal neurons from IR injury. IR-induced microgliosis and astrogliosis were suppressed by aucubin treatment. IR-induced increases in IL1β and TNFα levels were significantly alleviated by the treatment. IR-induced upregulation of TLR4 and downregulation of IκBα were significantly prevented by aucubin treatment, and IR-induced nuclear translocation of NF-κB was reversed by aucubin treatment. Briefly, aucubin exhibited neuroprotective effects against brain IR injury, which might be related to the attenuation of neuroinflammation through inhibiting the TLR-4/NF-κB signaling pathway. These results suggest that aucubin pretreatment may be a potential approach for the protection of brain IR injury. Full article

(This article belongs to the Special Issue New Molecular Insights into Ischemia/Reperfusion)

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Review

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18 pages, 2797 KiB

Open AccessReview

Detrimental Roles of Hypoxia-Inducible Factor-1α in Severe Hypoxic Brain Diseases

by Yoon Kyung Choi

Int. J. Mol. Sci. 2024, 25(8), 4465; https://doi.org/10.3390/ijms25084465 - 18 Apr 2024

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Abstract

Hypoxia stabilizes hypoxia-inducible factors (HIFs), facilitating adaptation to hypoxic conditions. Appropriate hypoxia is pivotal for neurovascular regeneration and immune cell mobilization. However, in central nervous system (CNS) injury, prolonged and severe hypoxia harms the brain by triggering neurovascular inflammation, oxidative stress, glial activation, vascular damage, mitochondrial dysfunction, and cell death. Diminished hypoxia in the brain improves cognitive function in individuals with CNS injuries. This review discusses the current evidence regarding the contribution of severe hypoxia to CNS injuries, with an emphasis on HIF-1α-mediated pathways. During severe hypoxia in the CNS, HIF-1α facilitates inflammasome formation, mitochondrial dysfunction, and cell death. This review presents the molecular mechanisms by which HIF-1α is involved in the pathogenesis of CNS injuries, such as stroke, traumatic brain injury, and Alzheimer’s disease. Deciphering the molecular mechanisms of HIF-1α will contribute to the development of therapeutic strategies for severe hypoxic brain diseases. Full article

(This article belongs to the Special Issue New Molecular Insights into Ischemia/Reperfusion)

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19 pages, 2021 KiB

Open AccessReview

Metabolic Considerations in Direct Procurement and Perfusion Protocols with DCD Heart Transplantation

by Maria Arnold, Peter Do, Sean M. Davidson, Stephen R. Large, Anja Helmer, Georgia Beer, Matthias Siepe and Sarah L. Longnus

Int. J. Mol. Sci. 2024, 25(8), 4153; https://doi.org/10.3390/ijms25084153 - 09 Apr 2024

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Abstract

Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike conventional grafts obtained through donation after brain death, DCD cardiac grafts are not only exposed to warm, unprotected ischemia, but also to a potentially damaging pre-ischemic phase after withdrawal of life-sustaining therapy (WLST). In this review, we aim to bring together knowledge about changes in cardiac energy metabolism and its regulation that occur in DCD donors during WLST, circulatory arrest, and following the onset of warm ischemia. Acute metabolic, hemodynamic, and biochemical changes in the DCD donor expose hearts to high circulating catecholamines, hypoxia, and warm ischemia, all of which can negatively impact the heart. Further metabolic changes and cellular damage occur with reperfusion. The altered energy substrate availability prior to organ procurement likely plays an important role in graft quality and post-ischemic cardiac recovery. These aspects should, therefore, be considered in clinical protocols, as well as in pre-clinical DCD models. Notably, interventions prior to graft procurement are limited for ethical reasons in DCD donors; thus, it is important to understand these mechanisms to optimize conditions during initial reperfusion in concert with graft evaluation and re-evaluation for the purpose of tailoring and adjusting therapies and ensuring optimal graft quality for transplantation. Full article

(This article belongs to the Special Issue New Molecular Insights into Ischemia/Reperfusion)

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22 pages, 2050 KiB

Open AccessReview

Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury

by Vyacheslav V. Ryabov, Leonid N. Maslov, Evgeniy V. Vyshlov, Alexander V. Mukhomedzyanov, Mikhail Kilin, Svetlana V. Gusakova, Alexandra E. Gombozhapova and Oleg O. Panteleev

Int. J. Mol. Sci. 2024, 25(2), 897; https://doi.org/10.3390/ijms25020897 - 11 Jan 2024

Cited by 1 | Viewed by 1435

Abstract

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased in recent years. The leading cause of death of these patients is ischemia/reperfusion (I/R) cardiac injury. It is quite obvious that there is an urgent need to create new drugs for the treatment of STEMI based on knowledge about the pathogenesis of I/R cardiac injury, in particular, based on knowledge about the molecular mechanism of ferroptosis. In this study, it was demonstrated that ferroptosis is involved in the development of I/R cardiac injury, antitumor drug-induced cardiomyopathy, diabetic cardiomyopathy, septic cardiomyopathy, and inflammation. There is indirect evidence that ferroptosis participates in stress-induced cardiac injury. The activation of AMPK, PKC, ERK1/2, PI3K, and Akt prevents myocardial ferroptosis. The inhibition of HO-1 alleviates myocardial ferroptosis. The roles of GSK-3β and NOS in the regulation of ferroptosis require further study. The stimulation of Nrf2, STAT3 prevents ferroptosis. The activation of TLR4 and NF-κB promotes ferroptosis of cardiomyocytes. MiR-450b-5p and miR-210-3p can increase the tolerance of cardiomyocytes to hypoxia/reoxygenation through the inhibition of ferroptosis. Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p and miR-15a-5p can aggravate myocardial ferroptosis. Full article

(This article belongs to the Special Issue New Molecular Insights into Ischemia/Reperfusion)

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