NADPH Oxidases and Blood-Brain Barrier Dysfunction in Stroke

Kahles, Timo; Heumüller, Sabine; Brandes, Ralf P.

doi:10.1007/978-1-60761-600-9_11

Cited by 2 publications

(2 citation statements)

References 112 publications

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“…Many animal models of neurological diseases with involvement of the cerebral vasculature, such as Alzheimer's disease [52][53][54] or ischemic stroke (reviewed by [55]), as well as models of stroke-related risk factors [56][57][58] have shown a diseaseassociated increase in ROS formation and signs of attenuated endothelial function (reviewed by [59]). Indeed, various effects of ROS on the vasculature have been demonstrated, including inhibition of the regulation of vascular tone and cerebral blood flow (reviewed by [59,60]), impairment of thromboresistance by altering platelet activation [61], and alterations of the BBB integrity (reviewed by [62,63]). …”

Section: Ros In Ischemic Brain Injurymentioning

confidence: 99%

“…Despite different pathogenic mechanisms, oxidative stress and increased BBB permeability are common findings in several diseases of the CNS (further discussed in [63]), leading to discussions on whether BBB disruption simply coincides with oxidative stress or whether it is a consequence of increased ROS formation. Many experimental neuroprotection studies on antioxidant approaches have found that antioxidants do have beneficial effects on the maintenance of BBB integrity during I/R, pointing to a causal relationship between oxidative stress and BBB disturbances.…”

Section: Ros In Ischemic Brain Injurymentioning

confidence: 99%

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NADPH oxidases as therapeutic targets in ischemic stroke

Kahles

Brandes

2012

Cell. Mol. Life Sci.

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117

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Reactive oxygen species (ROS) act physiologically as signaling molecules. In pathological conditions, such as ischemic stroke, ROS are released in excessive amounts and upon reperfusion exceed the body's antioxidant detoxifying capacity. This process leads to brain tissue damage during reoxygenation. Consequently, antioxidant strategies have long been suggested as a therapy for experimental stroke, but clinical trials have not yet been able to promote the translation of this concept into patient treatment regimens. As an evolution of this concept, recent studies have targeted the sources of ROS generation-rather than ROS themselves. In this context, NADPH oxidases have been identified as important generators of ROS in the cerebral vasculature under both physiological conditions in general and during ischemia/reoxygenation in particular. Inhibition of NADPH oxidases or genetic deletion of certain NADPH oxidase isoforms has been found to considerably reduce ischemic injury in experimental stroke. This review focuses on recent advances in the understanding of NADPH oxidase-mediated tissue injury in the cerebral vasculature, particularly at the level of the blood-brain barrier, and highlights promising inhibitory strategies that target the NADPH oxidases.

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Section: Ros In Ischemic Brain Injurymentioning

confidence: 99%

Section: Ros In Ischemic Brain Injurymentioning

confidence: 99%

NADPH oxidases as therapeutic targets in ischemic stroke

Kahles

Brandes

2012

Cell. Mol. Life Sci.

Self Cite

117

View full text Add to dashboard Cite

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Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats

Marín‐Prida

Liberato

Llopiz

et al. 2022

CPD

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Background: Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options. Objective: This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes on the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis. Methods: : Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Neurological, behavioral and histochemical parameters were assessed in I/R rats at 24 h. Cerebral gene expression and hippocampal neuron viability were evaluated in hypoperfused rats at acute (24 h) or chronic phases (30 days), respectively. A molecular docking analysis between NOX2 and C-PC-derived Phycocyanobilin (PCB) was also performed. Results: C-PC, obtained with a purity of 4.342, significantly reduced the infarct volume and neurologic deficit in a dose-dependent manner, and improved the exploratory activity of the I/R rats. This biliprotein inhibited NOX2 expression, a crucial NAPDH oxidase isoform in the brain, and the superoxide increase produced by the ischemic event. Moreover, C-PC-derived PCB showed a high binding affinity in silico with NOX2. C-PC downregulated the expression of pro-inflammatory genes (IFN-γ, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-β) in hypoperfused brain areas. This compound also decreased chronic neuronal death in the hippocampus of hypoperfused rats. Conclusion: These results suggest that the inhibition of cerebral NADPH oxidase and the improvement of neuroinflammation are key mechanisms mediating the neuroprotective actions of C-PC against brain ischemia.

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NADPH Oxidases and Blood-Brain Barrier Dysfunction in Stroke

Cited by 2 publications

References 112 publications

NADPH oxidases as therapeutic targets in ischemic stroke

NADPH oxidases as therapeutic targets in ischemic stroke

Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats

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