Cited by 125Redox biology and oxidative stressNitric Oxide and Endothelin EffectsNeurological Disorders and Treatments

Which NADPH Oxidase Isoform Is Relevant for Ischemic Stroke? The Case for Nox 2

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Kahles, Timo, Brandes, Ralf P.·2013·Antioxidants & Redox Signaling

Abstract

UNLABELLED: Significance and Recent Advances: Ischemic stroke is the leading cause of disability and third in mortality in industrialized nations. Immediate restoration of cerebral blood flow is crucial to salvage brain tissue, but only few patients are eligible for recanalization therapy. Thus, the need for alternative neuroprotective strategies is huge, and antioxidant interventions have long been studied in this context. Reactive oxygen species (ROS) physiologically serve as signaling molecules, but excessive amounts of ROS, as generated during ischemia/reperfusion (I/R), contribute to tissue injury. CRITICAL ISSUES: Nevertheless and despite a strong rational of ROS being a pharmacological target, all antioxidant interventions failed to improve functional outcome in human clinical trials. Antioxidants may interfere with physiological functions of ROS or do not reach the crucial target structures of ROS-induced injury effectively. FUTURE DIRECTIONS: Thus, a potentially more promising approach is the inhibition of the source of disease-promoting ROS. Within recent years, NADPH oxidases (Nox) of the Nox family have been identified as mediators of neuronal pathology. As, however, several Nox homologs are expressed in neuronal tissue, and as many of the pharmacological inhibitors employed are rather unspecific, the concept of Nox as mediators of brain damage is far from being settled. In this review, we will discuss the contribution of Nox homologs to I/R injury at large as well as to neuronal damage in particular. We will illustrate that the current data provide evidence for Nox2 as the most important NADPH oxidase mediating cerebral injury.

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Crossref · 10.1089/ars.2012.4721

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  • Increased NOX2 activity is linked to vascular disease.

    “The current knowledge about NOX enzymes in the cardiovascular system indicates that NOX2 is usually the main player in the development of pathological conditions and increased NOX2 activity is linked to vascular disease (142, 252, 478).”
  • Current knowledge about NOX enzymes in the cardiovascular system indicates that NOX2 is usually the main player in the development of pathological conditions.

    “The current knowledge about NOX enzymes in the cardiovascular system indicates that NOX2 is usually the main player in the development of pathological conditions and increased NOX2 activity is linked to vascular disease (142, 252, 478).”

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  1. [35]Choi DH. Lee KH. Kim MY. Han SH. Lee J. Role of NADPH oxidase 1 in ischemia/reperfusion- induced brain injury after stroke. Abstract presented at 25th International Symposium on Cerebral Blood Flow, Metabolism and Function; Barcelona, Spain. 2011. [Google Scholar]

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Authors
Kahles, T., & Brandes, R. P.
Affiliations
Goethe University Frankfurt (DE)
Venue
Antioxidants & Redox Signaling
Published
2013-04-20
Volume
18
Issue
12
Pages
1400-1417
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W2007066669
Cited by
125
References
201
Citations by year
2026: 5 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 9 · 2020: 7 · 2019: 11 · 2018: 12 · 2017: 11 · 2016: 15 · 2015: 10 · 2014: 8 · 2013: 6 · 2012: 4
FWCI
0.82
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft (SFB 815, SFB,834, KA2279/4-1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
NADPH oxidase, NOX2, ischemic stroke, ischemia-reperfusion injury, reactive oxygen species, neuroprotection, antioxidant therapy, neuronal injury, cerebral blood flow, NOX inhibitors
MeSH terms
NADPH Oxidase 2, Animals, Brain, Cerebral Arteries, Brain Ischemia, Humans, Isoenzymes, Membrane Glycoproteins, Neurons, Reperfusion Injury, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Stroke

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