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Immune Response to Cerebral Ischemia: Exploring Mechanisms and Potential Treatment Targets

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (10 August 2023) | Viewed by 2451

Special Issue Editor


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Guest Editor
Department of Physiology, Universitat de València, 46003 Valencia, Spain
Interests: stroke; ischemia cerebral; inflammation; pathophysiology; DAMPs; PRRs; systemic immunity; microglia

Special Issue Information

Dear Colleagues,

Stroke continues to be the second leading cause of mortality worldwide, being responsible for 1 of every 10 deaths, equivalent to about 5–6 million deaths per year. In addition, a similar number of patients become permanently disabled due to strokes, making this disease the leading cause of permanent physical disability. With treatments for ischemic stroke still limited to clot lysis and/or mechanical removal, new therapeutic targets are desperately needed.

Inflammation plays a central and dual role in the pathophysiology of stroke: on one hand, it participates in the development of ischemic damage in the early stages, and on the other it prepares the affected tissue for remodeling and reparation in later phases. The cellular and molecular mediators involved in the inflammatory response after stroke, as well as the interactions between them, are numerous and highly complex. Inflammation begins at the time of arterial occlusion when ischemic neurons release damage-associated molecular patterns (DAMPs). These molecules bind to pattern recognition receptors (PRRs), which are expressed in many cell types of the immune system. Of special relevance are the microglia, the resident macrophage immune cells of the central nervous system, whose main function is to regulate brain development, maintain neuronal networks, and contribute to neurorepair processes.

Despite the promising results obtained in experimental studies, all treatments modulators of the inflammatory response have failed in clinical trials.

This Special Issue on “Immune Response to Cerebral Ischemia: Exploring Mechanisms and Potential Treatment Targets” welcomes original research articles and reviews in this field, with a focus on all aspects of molecular mechanisms and potential treatment targets, for developing new research approaches as well as therapeutic strategies.

Potential topics include, but are not limited to:

  • Recent advances related to the dynamic changes and time-dependent role of inflammatory mediators employed in post-stroke inflammatory response that could help in diagnostic, therapeutic and prognostic strategies.
  • Potential signaling mechanisms of action that shift immune responses from detrimental to beneficial protective effects after cerebral ischemia.
  • State-of-the-art advances focused on answering questions about the interaction between changes in systemic immunity (lymphoid organs and the gut) and the impact on the brain post-stroke infections.
  • Animal and human studies addressing the role of adaptive immunity and chronic inflammation on the poorly studied, long-term neuropsychiatric sequelae of stroke.

Research to improve the ability to mimic the complexity of human trials by using stroke models studying both sexes, including aging and long-term sequelae, comparable to those of clinical trials, will be particularly valuable for the advancement of stroke therapy.

For submissions to this Special Issue, pure clinical research does not meet our journal’s aim and scope; nevertheless, clinical data added with molecular mechanical studies will be warmly welcomed.

Dr. Maria Consuelo Burguete
Guest Editor

Manuscript Submission Information

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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

  • stroke
  • ischemia cerebral
  • inflammation
  • pathophysiology
  • DAMPs
  • PRRs
  • systemic immunity
  • microglia

Published Papers (1 paper)

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Research

15 pages, 1923 KiB  
Article
Characterization of the Involvement of Tumour Necrosis Factor (TNF)-α-Stimulated Gene 6 (TSG-6) in Ischemic Brain Injury Caused by Middle Cerebral Artery Occlusion in Mouse
by Chiara Di Santo, Daniele La Russa, Rosaria Greco, Alessandra Persico, Anna Maria Zanaboni, Giacinto Bagetta and Diana Amantea
Int. J. Mol. Sci. 2023, 24(6), 5800; https://doi.org/10.3390/ijms24065800 - 18 Mar 2023
Cited by 2 | Viewed by 1909
Abstract
The identification of novel targets to modulate the immune response triggered by cerebral ischemia is crucial to promote the development of effective stroke therapeutics. Since tumour necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, is involved in the regulation of immune [...] Read more.
The identification of novel targets to modulate the immune response triggered by cerebral ischemia is crucial to promote the development of effective stroke therapeutics. Since tumour necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, is involved in the regulation of immune and stromal cell functions in acute neurodegeneration, we aimed to characterize its involvement in ischemic stroke. Transient middle cerebral artery occlusion (1 h MCAo, followed by 6 to 48 of reperfusion) in mice resulted in a significant elevation in cerebral TSG-6 protein levels, mainly localized in neurons and myeloid cells of the lesioned hemisphere. These myeloid cells were clearly infiltrating from the blood, strongly suggesting that brain ischemia also affects TSG-6 in the periphery. Accordingly, TSG-6 mRNA expression was elevated in peripheral blood mononuclear cells (PBMCs) from patients 48 h after ischemic stroke onset, and TSG-6 protein expression was higher in the plasma of mice subjected to 1 h MCAo followed by 48 h of reperfusion. Surprisingly, plasma TSG-6 levels were reduced in the acute phase (i.e., within 24 h of reperfusion) when compared to sham-operated mice, supporting the hypothesis of a detrimental role of TSG-6 in the early reperfusion stage. Accordingly, systemic acute administration of recombinant mouse TSG-6 increased brain levels of the M2 marker Ym1, providing a significant reduction in the brain infarct volume and general neurological deficits in mice subjected to transient MCAo. These findings suggest a pivotal role of TSG-6 in ischemic stroke pathobiology and underscore the clinical relevance of further investigating the mechanisms underlying its immunoregulatory role. Full article
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