Hany E. Marei
Changjun Yang
Carlo Cenciarelli
Assia Jaillard- 1Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
- 2Department of Neuroscience, University of Florida, Gainesville, FL, United States
- 3Institute of Translational Pharmacology (IFT)-CNR, Rome, Italy
- 4Université Grenoble Alpes Saint Martin d'Hères, Grenoble, France
Editorial on the Research Topic
Inflammation in ischemic stroke and novel therapeutic strategies for stroke treatment
Stroke is one of the leading causes of death and long-term disability worldwide (1). An ischemic stroke occurs when a major cerebral blood vessel becomes blocked, depriving downstream tissue of oxygen and nutrients and resulting in cell death within minutes at the core of the infarct. Dying cells release pro-inflammatory signals, which activate resident astrocytes/microglia and initiate immune cell infiltration from the periphery into the damaged tissue, contributing to blood–brain barrier disruption and exacerbating cell death in a process known as secondary inflammation, which can last for days to weeks after the initial insult (2). The premise of tissue repair in acute ischemic stroke is the proper termination of cell-death-induced neural inflammation (AIS). Macrophages scavenge cell corpses and produce inflammatory mediators that coordinate immune responses (3).
Stem cell therapy is a hot research area and a promising clinical therapeutic modality for ischemic stroke. Cell-engineering approaches are expected to usher in a new generation of stem cell-based therapies, greatly expanding their therapeutic utility for a variety of traumatic and neurodegenerative diseases, including ischemic stroke (4).
This Research Topic includes five manuscripts that highlight current knowledge and future directions in the role of neuroinflammation and the potential use of cell-based therapies in ischemic stroke. Zhou et al. look into whether L-4F displays neurorestorative benefits in the ischemic brain and the underlying molecular mechanisms after stroke in type 2 diabetes mellitus (T2DM). They concluded that administering L-4F post-stroke may provide a restorative strategy for type 2 diabetes mellites (T2DM)-stroke by promoting neurovascular and white matter (WM) remodeling. Reducing neuroinflammation in the injured brain may aid the restorative effects of L-4F that are not mediated by the ABCA1 signaling pathway (Zhou et al.). Yu et al. have looked at the effects of metformin, rapamycin, and nicotinamide mono nucleotide (NMN) on cognitive function, white matter integrity, microglial response, and phagocytosis in a rat model of vascular cognitive impairment (VCI) caused by bilateral common carotid artery occlusion (BCCAO). According to the findings, metformin, rapamycin, or NMN may protect or mitigate cognitive impairment and WMLs by modifying microglial polarization and inhibiting phagocytosis. The findings could pave the way for a new approach to VCI treatment (Yu et al.). Zhao et al. compared the remote ischemic postconditioning (RIPostC) group to a control group in a meta-analysis of eligible randomized controlled trials in patients with ischemic stroke. They concluded that RIPostC is safe and effective, with a positive cerebral protective effect in patients with ischemic stroke, and that large-sample, multicenter trials are needed to validate RIPostC's cerebral protective effect in the future (5). Custodia et al. review the most recent advances in preclinical and clinical research on the use of endothelial progenitor cells (EPCs) after stroke, not only as a single treatment but also in combination with novel therapeutic approaches. Following cerebrovascular damage, EPCs can repair damaged vessels as well as generate new ones. EPCs are circulating cells that have endothelial cell and adult stem cell characteristics, including the ability to differentiate into mature endothelial cells and self-renew. Furthermore, EPCs have the advantage of already being present in healthy conditions as circulating cells that participate in endothelial maintenance in a direct and paracrine manner. Based on clinical data demonstrating a better neurological and functional outcome in ischemic stroke patients with higher levels of circulating EPCs, novel and promising therapeutic approaches would be EPCs-promoting pharmacological treatments as well as EPCs-based therapies (5). In rodent stroke models, Satani et al. have proposed that systemic administration of marrow stromal cells (MSCs) causes the release of a wide range of factors that mediate recovery. In this study they have investigated the immunomodulatory interactions between MSCs and peripheral blood-derived monocytes (Mo) obtained from acute stroke patients. This study found MSCs had a differential effect on Mo derived from acute stroke patients vs. those derived from healthy controls, suggesting that immunomodulation of immune cells may represent a therapeutic target for MSCs in patients with acute stroke (Satani et al.).
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Feigin VL, Stark BA, Johnson CO, Roth GA, Bisignano C, Abady GG, et al. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. (2021) 20:795–820. doi: 10.1016/S1474-4422(21)00252-0
2. Jayaraj RL, Azimullah S, Beiram R, Jalal FY, Rosenberg AG. Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammat. (2019) 16:1–24. doi: 10.1186/s12974-019-1516-2
3. Cai W, Hu M, Li C, Wu R, Lu D, Xie C, et al. FOXP3+ macrophage represses acute ischemic stroke-induced neural inflammation. Autophagy. (2022) 1–20. doi: 10.1080/15548627.2022.2116833. [Epub ahead of print].
4. Kimbrel EA, Lanza R. Next-generation stem cells—ushering in a new era of cell-based therapies. Nat Rev Drug Discovery. (2020) 19:463–79. doi: 10.1038/s41573-020-0064-x
Keywords: ischemic stroke, neuroinflammation, blood–brain barrier, oxidative stress, stem cells
Citation: Marei HE, Yang C, Cenciarelli C and Jaillard A (2022) Editorial: Inflammation in ischemic stroke and novel therapeutic strategies for stroke treatment. Front. Neurol. 13:1071557. doi: 10.3389/fneur.2022.1071557
Received: 16 October 2022; Accepted: 26 October 2022;
Published: 18 November 2022.
Edited and reviewed by: Leonard Verhagen Metman, Rush University, United States
Copyright © 2022 Marei, Yang, Cenciarelli and Jaillard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Hany E. Marei, hanymarei@mans.edu.eg; Carlo Cenciarelli, cencia65@gmail.com