Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke‐Induced Oxidative Stress

Duan, Jinnan; Gao, Shiqi; Tu, Sheng; Lenahan, Cameron; Shao, Anwen; Sheng, Jifang

doi:10.1155/2021/6631805

Cited by 47 publications

(37 citation statements)

References 74 publications

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“…NOX5 upregulation and activation is related with many different processes, including the unfolded protein response [ 39 ], the management of lipid accumulation and insulin sensitivity [ 40 ] or the inflammation via COX2 activation and PG pathway induction [ 22 ]. In this context, the COX2 pathway may lead to brain ROS accumulation during aging [ 41 ] or after stroke [ 42 ]. In this work, we found that cerebral NOX5 expression in our knock-in mice led to an increase in the COX2 mRNA levels compared to the Control Young group.…”

Section: Discussionmentioning

confidence: 99%

Expression of Endothelial NOX5 Alters the Integrity of the Blood-Brain Barrier and Causes Loss of Memory in Aging Mice

et al. 2021

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Blood-Brain barrier (BBB) disruption is a hallmark of central nervous system (CNS) dysfunction, and oxidative stress is one of the molecular mechanisms that may underlie this process. NADPH oxidases (NOX) are involved in oxidative stress-mediated vascular dysfunction and participate in the pathophysiology of its target organs. The NADPH oxidase 5 (NOX5) isoform is absent in rodents, and although little is known about the role it may play in disrupting the BBB, it has recently been implicated in experimental stroke. Our aim was to investigate the role of NADPH oxidase 5 (NOX5) in promoting vascular alterations and to identify its impact on the cognitive status of aged mice. No differences were detected in the arterial blood pressure or body weight between knock-in mice expressing endothelial NOX5 and the control mice. The Morris water maze test showed memory impairments in the aged knock-in mice expressing NOX5 compared with their control littermates. For assessing the BBB integrity, we studied the protein expression of two tight junction (TJ) proteins: Zonula occludens-1 (ZO-1) and occludin. Compared to the control animals, Aged NOX5 mice exhibited reduced levels of both proteins, demonstrating an alteration of the BBB integrity. Our data indicate that vascular NOX5 may favor behavioral changes with aging through oxidative stress-mediated BBB breakdown.

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Section: Discussionmentioning

confidence: 99%

Expression of Endothelial NOX5 Alters the Integrity of the Blood-Brain Barrier and Causes Loss of Memory in Aging Mice

et al. 2021

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“…VAS2870 is a pharmacological inhibitor of NOX and has been shown to decrease infarct volume, oxidative stress, neuronal apoptosis and BBB leakage [ 36 ]. Several new small-molecule NOX inhibitors have been recently identified, such as VAS2970, M13, GKT136901, ML090 and MLM171 [ 37 , 38 , 39 , 40 ]. They have the potential to reduce ROS production and inhibit brain tissue damage [ 40 ].…”

Section: Antioxidant Treatment Strategies Of Oxidative Stress In Strokementioning

confidence: 99%

“…Several new small-molecule NOX inhibitors have been recently identified, such as VAS2970, M13, GKT136901, ML090 and MLM171 [ 37 , 38 , 39 , 40 ]. They have the potential to reduce ROS production and inhibit brain tissue damage [ 40 ]. The NOX inhibitors are non-specific and not isoform selective, although it may not be particularly important in stroke treatment, the development of selective NOX inhibitors could provide information about the precise role of various NOX isoforms.…”

Section: Antioxidant Treatment Strategies Of Oxidative Stress In Strokementioning

confidence: 99%

Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

2021

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The production of free radicals is inevitably associated with metabolism and other enzymatic processes. Under physiological conditions, however, free radicals are effectively eliminated by numerous antioxidant mechanisms. Oxidative stress occurs due to an imbalance between the production and elimination of free radicals under pathological conditions. Oxidative stress is also associated with ageing. The brain is prone to oxidative damage because of its high metabolic activity and high vulnerability to ischemic damage. Oxidative stress, thus, plays a major role in the pathophysiology of both acute and chronic pathologies in the brain, such as stroke, traumatic brain injury or neurodegenerative diseases. The goal of this article is to summarize the basic concepts of oxidative stress and its significance in brain pathologies, as well as to discuss treatment strategies for dealing with oxidative stress in stroke.

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“…Upon cerebral ischemia, the mitochondrial respiratory chain is damaged and ATP synthesis is reduced, which is accompanied by the excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [23]. In addition, activated microglia can increase the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, inducing the generation of ROS [24,25]. ROS has been reported to accumulate in ischemic tissue; its strong oxidation ability leads to the peroxidation of lipids, proteins and unsaturated fatty acids on the basement membrane and destroys the blood-brain barrier (BBB), ultimately causing irreversible damages on nucleic acid and carbohydrate metabolism [26,27].…”

Section: Oxidative Stressmentioning

confidence: 99%

Research progress of natural products for the treatment of ischemic stroke

Li¹,

Zhao²,

Qiao³

et al. 2022

J. Integr. Neurosci.

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Stroke is a leading cause of death and disability world-widely. The incidence rate of stroke has been increasing due to the aging population and lifestyle changes. At present, the only drug approved by the US Food and Drug Administration (FDA) for the treatment of ischemic stroke is tissue plasminogen activator (t-PA), but its clinical application is greatly limited because of its narrow time window and bleeding risk. Natural products have a long history of being used in traditional medicine with good safety, making them an important resource for the development of new drugs. Indeed, some natural products can target a variety of pathophysiological processes related to stroke, including oxidative stress, in lammation and neuronal apoptosis. Therefore, the development of high-e ficiency, lowtoxicity, safe and cheap active substances from natural products is of great significance for improving the treatment alternatives of patients with stroke. This article reviews the neuroprotective e fects of 33 natural compounds by searching recent related literature. Among them, puerarin, pinocembrin, quercetin, epigallocatechin-3-gallate (EGCG), and resveratrol have great potential in the clinical treatment of ischemic stroke. This review will provide a powerful reference for screening natural compounds with potential clinical application value in ischemic stroke or synthesizing new neuroprotective agents with natural compounds as lead compounds.

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Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke‐Induced Oxidative Stress

Cited by 47 publications

References 74 publications

Expression of Endothelial NOX5 Alters the Integrity of the Blood-Brain Barrier and Causes Loss of Memory in Aging Mice

Expression of Endothelial NOX5 Alters the Integrity of the Blood-Brain Barrier and Causes Loss of Memory in Aging Mice

Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

Research progress of natural products for the treatment of ischemic stroke

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