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Antioxidants
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Translation of Antioxidant Therapies to the Clinical Arena of Ischemic...
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Translation of Antioxidant Therapies to the Clinical Arena of Ischemic Stroke

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (20 June 2025) | Viewed by 6752

Special Issue Editors

Dr. María Castelló-Ruiz

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Guest Editor
Department of Cell Biology, Functional Biology and Physical Anthropology, Faculty of Biology, Universitat de València, Burjassot, 46100 Valencia, Spain
Interests: Ischaemic stroke; cellular senescence; cerebroprotection; oestrogens; ageing; inflammation
Special Issues, Collections and Topics in MDPI journals
Dr. Juan B. Salom

E-Mail Website
Guest Editor
Unidad Mixta de Investigación Cerebrovascular, Instituto de Investigación Sanitaria La Fe, Universidad de Valencia, 46026 Valencia, Spain
Interests: stroke; cerebroprotection; oxidative stress; inflammation; cell senescence; animal models
Dr. Irene Escudero-Martínez

E-Mail Website
Guest Editor
Department of Neurology, Hospital Universitari i Politécnic La Fe, 46026 Valencia, Spain
Interests: stroke; endovascular treatment; reperfusion; cerebroprotection; microbiota

Special Issue Information

Dear Colleagues,

Stroke is the second most common cause of death and the major cause of adult physical permanent disability worldwide. This is a serious life-threating medical condition that occurs when the blood flow to part of the brain is interrupted, either by the blockage of a blood vessel (ischemic stroke), or by its rupture (haemorrhagic stroke).

Ischemic stroke triggers a cascade of complex molecular and cellular events, in which oxidative/nitrosative stress is one of the major players. The increase in free radical production associated with stroke induces lipid peroxidation, protein oxidation and DNA damage, which could lead to apoptosis and necrosis in brain cells. Additionally, oxidative stress contributes to triggering an inflammatory response and alteration of the blood–brain barrier permeability. Currently, therapeutic options for the acute treatment of stroke are aimed at rapid recanalization of the occluded vessel, either by thrombectomy alone or in combination with fibrinolysis. However, these strategies, although effective for the restoration of brain perfusion and metabolic activity, are also associated with a large burst of free radical production, which in turn, leads to increased oxidative stress, and secondary brain tissue damage. Recent early-phase clinical trials have shown promising results about the safety and cerebroprotective efficacy of antioxidant or anti-inflammatory drugs in stroke patients subjected to endovascular treatment. Therefore, there is room for good quality preclinical and clinical research on new or well-known antioxidant treatments to revisit cerebroprotection in the brain reperfusion era.

In this Special Issue, we invite researchers to provide reviews, original preclinical research articles, and clinical interventional or observational studies related to the use of antioxidant therapeutic approaches in the treatment of stroke. We welcome contributions on the role of oxidative stress in the damage of the ischemic/reperfused brain tissue, as well as novel findings on the use of treatments fostering endogenous antioxidant pathways or exogenous synthetic or natural antioxidants as cerebroprotectants in ischemic stroke.

Dr. María Castelló-Ruiz
Dr. Juan B. Salom
Dr. Irene Escudero-Martínez
Guest Editors

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. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Ischemic stroke
  • endovascular treatment
  • reperfusion
  • oxidative stress
  • cerebroprotectants
  • antioxidant therapeutic approaches

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Published Papers (3 papers)

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Research

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22 pages, 4616 KiB  
Article
In Vitro Modulation of Autophagy by New Antioxidant Nitrones as a Potential Therapeutic Approach for the Treatment of Ischemic Stroke
by Sara Izquierdo-Bermejo, Beatriz Chamorro, María Dolores Martín-de-Saavedra, Miguel Lobete, Francisco López-Muñoz, José Marco-Contelles and María Jesús Oset-Gasque
Antioxidants 2024, 13(8), 946; https://doi.org/10.3390/antiox13080946 - 3 Aug 2024
Cited by 1 | Viewed by 1620
Abstract
Stroke is a leading cause of death worldwide, yet current therapeutic strategies remain limited. Among the neuropathological events underlying this disease are multiple cell death signaling cascades, including autophagy. Recent interest has focused on developing agents that target molecules involved in autophagy to [...] Read more.
Stroke is a leading cause of death worldwide, yet current therapeutic strategies remain limited. Among the neuropathological events underlying this disease are multiple cell death signaling cascades, including autophagy. Recent interest has focused on developing agents that target molecules involved in autophagy to modulate this process under pathological conditions. This study aimed to analyze the role of autophagy in cell death induced by an in vitro ischemia–reperfusion (IR) model and to determine whether nitrones, known for their neuroprotective and antioxidant effects, could modulate this process. We focused on key proteins involved in different phases of autophagy: HIF-1α, BNIP3, and BECN1 for induction and nucleation, LC3 for elongation, and p62 for degradation. Our findings confirmed that the IR model promotes autophagy, initially via HIF-1α activation. Additionally, the neuroprotective effect of three of the selected synthetic nitrones (quinolylnitrones QN6 and QN23, and homo-bis-nitrone HBN6) partially derives from their antiautophagic properties, demonstrated by a downregulation of the expression of molecular markers involved in various phases of autophagy. In contrast, the neuroprotective power of cholesteronitrone ChN2 seems to derive from its promoting effects on the initial phases of autophagy, which could potentially help inhibit other forms of cell death. These results underscore the importance of autophagy modulation in neuroprotection, highlighting the potential of inhibiting prodeath autophagy and promoting prosurvival autophagy as promising therapeutic approaches in treating ischemic stroke clinically. Full article
(This article belongs to the Special Issue Translation of Antioxidant Therapies to the Clinical Arena of Ischemic Stroke)
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16 pages, 2413 KiB  
Article
Intracarotid Infusion of Redox-Active Manganese Porphyrin, MnTnBuOE-2-PyP5+, following Reperfusion Improves Long-Term, 28-Day Post-Stroke Outcomes in Rats
by Xuan Li, Weina Duan, Li Du, Dongmei Chu, Peng Wang, Zhong Yang, Xingguang Qu, Zhenxing Yang, Ines Batinic-Haberle, Ivan Spasojevic, David S. Warner, James D. Crapo, Miriam M. Treggiari and Huaxin Sheng
Antioxidants 2023, 12(10), 1861; https://doi.org/10.3390/antiox12101861 - 13 Oct 2023
Cited by 1 | Viewed by 2120
Abstract
Endovascular mechanical thrombectomy, combined with a tissue plasminogen activator (t-PA), is efficacious as a standard care for qualifying ischemic stroke patients. However, > 50% of thrombectomy patients still have poor outcomes. Manganese porphyrins, commonly known as mimics of superoxide dismutases, are potent redox-active [...] Read more.
Endovascular mechanical thrombectomy, combined with a tissue plasminogen activator (t-PA), is efficacious as a standard care for qualifying ischemic stroke patients. However, > 50% of thrombectomy patients still have poor outcomes. Manganese porphyrins, commonly known as mimics of superoxide dismutases, are potent redox-active catalytic compounds that decrease oxidative/nitrosative stress and in turn decrease inflammatory responses, mitigating therefore the secondary injury of the ischemic brain. This study investigates the effect of intracarotid MnTnBuOE-2-PyP5+ (BMX-001) administration on long-term, 28-day post-stroke recovery in a clinically relevant setting. The 90 min of transient middle cerebral artery occlusion was performed in young, aged, male, female, and spontaneous hypertension rats. All physiological parameters, including blood pressure, blood gas, glucose, and temperature, were well controlled during ischemia. Either BMX-001 or a vehicle solution was infused through the carotid artery immediately after the removal of filament, mimicking endovascular thrombectomy, and was followed by 7 days of subcutaneous injection. Neurologic deficits and infarct volume were assessed at 28 days in a blinded manner. The effects of BMX-001 on the carotid arterial wall and blood–brain barrier permeability and its interaction with t-PA were assessed in normal rats. There were no intra-group differences in physiological variables. BMX-001-treated stroke rats regained body weight earlier, performed better in behavioral tests, and had smaller brain infarct size compared to the vehicle-treated group. No vascular wall damage and blood–brain barrier permeability changes were detected after the BMX-001 infusion. There was no drug interaction between BMX-001 and t-PA. Intracarotid BMX-001 infusion was safe, and it significantly improved stroke outcomes in rats. These findings indicate that BMX-001 is a candidate drug as an adjunct treatment for thrombectomy procedure to further improve the neurologic outcomes of thrombectomy patients. This study warrants further clinical investigation of BMX-001 as a new stroke therapy. Full article
(This article belongs to the Special Issue Translation of Antioxidant Therapies to the Clinical Arena of Ischemic Stroke)
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Review

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29 pages, 6833 KiB  
Review
Development of Pharmacological Strategies with Therapeutic Potential in Ischemic Stroke
by Alejandro Escobar-Peso, Emma Martínez-Alonso, Jaime Masjuan and Alberto Alcázar
Antioxidants 2023, 12(12), 2102; https://doi.org/10.3390/antiox12122102 - 12 Dec 2023
Cited by 6 | Viewed by 2118
Abstract
Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, with the social dependency that it generates being an important source of inequality. The lack of treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is [...] Read more.
Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, with the social dependency that it generates being an important source of inequality. The lack of treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is presented as a need. With this goal in mind, our research group’s collaborative studies into cerebral ischemia and subsequent reperfusion concluded that there is a need to develop compounds with antioxidant and radical scavenger features. In this review, we summarize the path taken toward the identification of lead compounds as potential candidates for the treatment of acute ischemic stroke. Evaluations of the antioxidant capacity, neuroprotection of primary neuronal cultures and in vivo experimental models of cerebral ischemia, including neurological deficit score assessments, are conducted to characterize the biological efficacy of the various neuroprotective compounds developed. Moreover, the initial results in preclinical development, including dose–response studies, the therapeutic window, the long-term neuroprotective effect and in vivo antioxidant evaluation, are reported. The results prompt these compounds for clinical trials and are encouraging regarding new drug developments aimed at a successful therapy for ischemic stroke. Full article
(This article belongs to the Special Issue Translation of Antioxidant Therapies to the Clinical Arena of Ischemic Stroke)
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